An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.
An autosomal dominant vascular anomaly characterized by telangiectases of the skin and mucous membranes and by recurrent gastrointestinal bleeding. This disorder is caused by mutations of a gene (on chromosome 9q3) which encodes endoglin, a membrane glycoprotein that binds TRANSFORMING GROWTH FACTOR BETA.
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A group of rare, idiopathic, congenital retinal vascular anomalies affecting the retinal capillaries. It is characterized by dilation and tortuosity of retinal vessels and formation of multiple aneurysms, with different degrees of leakage and exudates emanating from the blood vessels.
An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Impairment of the ability to coordinate the movements required for normal ambulation (WALKING) which may result from impairments of motor function or sensory feedback. This condition may be associated with BRAIN DISEASES (including CEREBELLAR DISEASES and BASAL GANGLIA DISEASES); SPINAL CORD DISEASES; or PERIPHERAL NERVOUS SYSTEM DISEASES.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Bleeding from the nose.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Keto-pyrans.
One of the two types of ACTIVIN RECEPTORS. They are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES. The major type II activin receptors are ActR-IIA and ActR-IIB.
Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the CAPILLARIES. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.
Complex cytotoxic antibiotic obtained from Streptomyces flocculus or S. rufochronmogenus. It is used in advanced carcinoma and causes leukopenia.
A mild form of LIMITED SCLERODERMA, a multi-system disorder. Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.
Established cell cultures that have the potential to propagate indefinitely.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
The process by which a DNA molecule is duplicated.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
An individual having different alleles at one or more loci regarding a specific character.
Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Compounds that inhibit cell production of DNA or RNA.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
A cell line derived from cultured tumor cells.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Proteins that specifically bind to IRON.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A state of elevated cardiac output due to conditions of either increased hemodynamic demand or reduced cardiac oxygen output. These conditions may include ANEMIA; ARTERIOVENOUS FISTULA; THYROTOXICOSIS; PREGNANCY; EXERCISE; FEVER; and ANOXIA. In time, compensatory changes of the heart can lead to pathological form of high cardiac output and eventual HEART FAILURE.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
One of the two types of ACTIVIN RECEPTORS or activin receptor-like kinases (ALK'S). There are several type I activin receptors. The major active ones are ALK-2 (ActR-IA) and ALK-4 (ActR-IB).
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
An individual in which both alleles at a given locus are identical.
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.
Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A characteristic symptom complex.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Biochemical identification of mutational changes in a nucleotide sequence.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Human COLORECTAL CARCINOMA cell line.
An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A general term for various neoplastic diseases of the lymphoid tissue.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.
Acquired degenerative dilation or expansion (ectasia) of normal BLOOD VESSELS, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the GASTROINTESTINAL TRACT leading to GASTROINTESTINAL HEMORRHAGE and ANEMIA.
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Mapping of the KARYOTYPE of a cell.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Congenital vascular anomalies in the brain characterized by direct communication between an artery and a vein without passing through the CAPILLARIES. The locations and size of the shunts determine the symptoms including HEADACHES; SEIZURES; STROKE; INTRACRANIAL HEMORRHAGES; mass effect; and vascular steal effect.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. (1/2256)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.  (+info)

Requirement of ATM in phosphorylation of the human p53 protein at serine 15 following DNA double-strand breaks. (2/2256)

Microinjection of the restriction endonuclease HaeIII, which causes DNA double-strand breaks with blunt ends, induces nuclear accumulation of p53 protein in normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this induction of p53 accumulation is not observed in ataxia telangiectasia (AT) fibroblasts. HaeIII-induced p53 protein in normal fibroblasts is phosphorylated at serine 15, as determined by immunostaining with an antibody specific for phosphorylated serine 15 of p53. This phosphorylation correlates well with p53 accumulation. Treatment with lactacystin (an inhibitor of the proteasome) or heat shock leads to similar levels of p53 accumulation in normal and AT fibroblasts, but the p53 protein lacks a phosphorylated serine 15. Following microinjection of HaeIII into lactacystin-treated normal fibroblasts, lactacystin-induced p53 protein is phosphorylated at serine 15 and stabilized even in the presence of cycloheximide. However, neither stabilization nor phosphorylation at serine 15 is observed in AT fibroblasts under the same conditions. These results indicate the significance of serine 15 phosphorylation for p53 stabilization after DNA double-strand breaks and an absolute requirement for ATM in this phosphorylation process.  (+info)

Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. (3/2256)

Both p53 and ATM are checkpoint regulators with roles in genetic stabilization and cancer susceptibility. ATM appears to function in the same DNA damage checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosis and tumor suppression in response to cell cycle dysregulation is unknown. In this study, we tested the role of murine ataxia telangiectasia protein (Atm) in a transgenic mouse brain tumor model in which p53-mediated apoptosis results in tumor suppression. These p53-mediated activities are induced by tissue-specific inactivation of pRb family proteins by a truncated simian virus 40 large T antigen in brain epithelium. We show that p53-dependent apoptosis, transactivation, and tumor suppression are unaffected by Atm deficiency, suggesting that signaling in the DNA damage pathway is distinct from that in the oncogene-induced pathway. In addition, we show that Atm deficiency has no overall effect on tumor growth and progression in this model.  (+info)

GADD45 induction of a G2/M cell cycle checkpoint. (4/2256)

G1/S and G2/M cell cycle checkpoints maintain genomic stability in eukaryotes in response to genotoxic stress. We report here both genetic and functional evidence of a Gadd45-mediated G2/M checkpoint in human and murine cells. Increased expression of Gadd45 via microinjection of an expression vector into primary human fibroblasts arrests the cells at the G2/M boundary with a phenotype of MPM2 immunopositivity, 4n DNA content and, in 15% of the cells, centrosome separation. The Gadd45-mediated G2/M arrest depends on wild-type p53, because no arrest was observed either in p53-null Li-Fraumeni fibroblasts or in normal fibroblasts coexpressed with p53 mutants. Increased expression of cyclin B1 and Cdc25C inhibited the Gadd45-mediated G2/M arrest in human fibroblasts, indicating that the mechanism of Gadd45-mediated G2/M checkpoint is at least in part through modulation of the activity of the G2-specific kinase, cyclin B1/p34(cdc2). Genetic and physiological evidence of a Gadd45-mediated G2/M checkpoint was obtained by using GADD45-deficient human or murine cells. Human cells with endogenous Gadd45 expression reduced by antisense GADD45 expression have an impaired G2/M checkpoint after exposure to either ultraviolet radiation or methyl methanesulfonate but are still able to undergo G2 arrest after ionizing radiation. Lymphocytes from gadd45-knockout mice (gadd45 -/-) also retained a G2/M checkpoint initiated by ionizing radiation and failed to arrest at G2/M after exposure to ultraviolet radiation. Therefore, the mammalian genome is protected by a multiplicity of G2/M checkpoints in response to specific types of DNA damage.  (+info)

A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. (5/2256)

Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. Much of our current understanding of checkpoints comes from genetic studies conducted in yeast. In the fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component of both the DNA damage and DNA replication checkpoints. The SpChk1 and SpCds1 protein kinases function downstream of SpRad3. SpChk1 is an effector of the DNA damage checkpoint and, in the absence of SpCds1, serves an essential function in the DNA replication checkpoint. SpCds1 functions in the DNA replication checkpoint and in the S phase DNA damage checkpoint. Human homologs of both SpRad3 and SpChk1 but not SpCds1 have been identified. Here we report the identification of a human cDNA encoding a protein (designated HuCds1) that shares sequence, structural, and functional similarity to SpCds1. HuCds1 was modified by phosphorylation and activated in response to ionizing radiation. It was also modified in response to hydroxyurea treatment. Functional ATM protein was required for HuCds1 modification after ionizing radiation but not after hydroxyurea treatment. Like its fission yeast counterpart, human Cds1 phosphorylated Cdc25C to promote the binding of 14-3-3 proteins. These findings suggest that the checkpoint function of HuCds1 is conserved in yeast and mammals.  (+info)

Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia. (6/2256)

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69-9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18-2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought.  (+info)

The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. (7/2256)

BACKGROUND: Drosophila embryogenesis is initiated by 13 rapid syncytial mitotic divisions that do not require zygotic gene activity. This maternally directed cleavage phase of development terminates at the midblastula transition (MBT), at which point the cell cycle slows dramatically, membranes surround the cortical nuclei to form a cellular blastoderm, and zygotic gene expression is first required. RESULTS: We show that embryos lacking Mei-41, a Drosophila homologue of the ATM tumor suppressor, proceed through unusually short syncytial mitoses, fail to terminate syncytial division following mitosis 13, and degenerate without forming cells. A similar cleavage-stage arrest is produced by mutations in grapes, which encodes a homologue of the Checkpoint-1 kinase. We present biochemical, cytological and genetic data indicating that Mei-41 and Grapes are components of a conserved DNA-replication/damage checkpoint pathway that triggers inhibitory phosphorylation of the Cdc2 kinase and mediates resistance to replication inhibitors and DNA-damaging agents. This pathway is nonessential during postembryonic development, but it is required to terminate the cleavage stage at the MBT. Cyclins are required for Cdc2 kinase activity, and mutations in cyclin A and cyclin B bypass the requirement for mei-41 at the MBT. These mutations do not restore wild-type syncytial cell-cycle timing or the embryonic replication checkpoint, however, suggesting that Mei-41-mediated inhibition of Cdc2 has an additional essential function at the MBT. CONCLUSIONS: The Drosophila DNA-replication/damage checkpoint pathway can be activated by externally triggered DNA damage or replication defects throughout the life cycle, and under laboratory conditions this inducible function is nonessential. During early embryogenesis, however, this pathway is activated by developmental cues and is required for the transition from maternal to zygotic control of development at the MBT.  (+info)

Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. (8/2256)

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.  (+info)

Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR). Phosphoantibodies to ATF2(490/8) reveal dose- and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with gamma-H2AX and MRN components into IR-induced foci (IRIF). Inhibition of ATF2 expression decreased recruitment of Mre11 to IRIF, abrogated S phase checkpoint, reduced activation of ATM, Chk1, and Chk2, and impaired radioresistance. ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity. ...
Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a ...
Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATMs potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% ...
DNA-damage checkpoints maintain genomic integrity by mediating a cell-cycle delay in response to genotoxic stress or stalled replication forks. In response to damage, the checkpoint kinase ATR phosphorylates and activates its effector kinase Chk1 in a process that critically depends on Claspin [1]. However, it is not known how exactly this kinase cascade is silenced. Here we demonstrate that the abundance of Claspin is regulated through proteasomal degradation. In response to DNA damage, Claspin is transiently stabilized, and its expression depends on Chk1 kinase activity. In addition, we show that Claspin is degraded upon mitotic entry, a process that depends on the β-TrCP-SCF ubiquitin ligase and Polo-like kinase-1 (Plk1). We demonstrate that Claspin interacts with both β-TrCP and Plk1 and that inactivation of these components or the β-TrCP recognition motif in Claspin prevents its mitotic degradation. Interestingly, expression of a nondegradable Claspin mutant inhibits recovery from a ...
Ataxia Telangiectasia Mutated protein kinase (ATM) has lately come to the fore as a regulatory protein fulfilling many roles within…. Continue Reading →. ...
In terms of the exploiting DDR pathway for therapeutic intervention, the inhibitors of Poly ADP-ribose polymerase-1 have made the greatest progress and many such inhibitors are currently valuated in clinical trials [228]. Following the initial discoveries of inhibitors of ATM [214, 217], the quest for finding compounds with higher specificity and to test them for their therapeutic benefit quickly followed. There are several reports that demonstrate increased cellular sensitivity towards genotoxic agents by way of modulating the ATM signalling pathway through inhibition of ATM kinase specifically. In one of the earliest of such reports, Morgan SE et al (1997) demonstrated that over-expression of a truncated version of the functionally important leucine zipper domain of the ATM gave rise to a dominant negative ATM mutant in colon cancer cells. This group reported that such cells had an increased level of radiosensitivity and chromosomal breakage and an abrogated S-phase checkpoint. Inhibition of ...
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Abstract Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the […]. ...
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(2012) Gannon et al. Cancer Cell. DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in v...
I think that its tricky to say. The effect of DNAPK inhibitor and ATM inhibitor was the same as that of caffeine in the case of MDC1, suggesting that DNAPK and ATM are both required for a response in that situation. DNA-PKcs is mainly recruited to DSB ends and activated by its regulatory subunit, Ku, which binds to ends (Together they make DNA-PK). (1) ATM on the other hand is recruited to DSBs and activated by MRN, which also binds ends. (2) All of these proteins separately bind MDC1 (DNA-PK, ATM, MRN). The authors used siRNAs against Ku, which did not display any abrogated focus formation, meaning that DNA-PKcs is not being recruited to the focus through Ku. It is not known where on DNA-PK MDC1 binds, but it does bind to the PST repeats on MDC1, which would make me think that it wouldnt inhibit other proteins (ATM, MRN) from binding. If I had to speculate, I would say that there is probably some complicated kinetics between ATM and DNAPK phosphorylation such that DNAPK phosphorylates H2AX ...
Stokes M (2007) CST Curation Set: 2262; Year: 2007; Biosample/Treatment: cell line, M059K/UV; Disease: glioblastoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 ...
Stokes M (2005) CST Curation Set: 909; Year: 2005; Biosample/Treatment: cell line, M059K/UV; Disease: glioblastoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 ...
Hi there Network as shown: Enduser -> eth-to-atm -> C7600 -> switch The enduser uses FastEthernet and have several VLANs. The "eth-to-atm" is a non-cisco based system capable of converting ethernet to atm cells and allowing baby
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Worlds most popular four-digit ATM PIN number combinations, like 1234, are the most dangerous combinations and can be guessed easily, reveals study.
The womans terrifying ordeal included her being forced to withdraw $500 from her ATM and later having a photo of her ID taken by the suspect.
Emergency responders discovered the infant in the rear of 130 W. 183rd St. near Sedgwick Ave. in University Heights, but she could no
Albany, US) DelveInsight has launched a new report on Ataxia Telangiectasia Pipeline. Ataxia Telangiectasia (AT) Pipeline Insight, 2020 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects across the Ataxia Telangiectasia (AT) market. A detailed picture of the Ataxia Telangiectasia (AT) pipeline landscape is provided, which includes the disease overview and Ataxia Telangiectasia (AT) treatment guidelines. The assessment part of the report embraces in-depth Ataxia Telangiectasia (AT) commercial assessment and clinical assessment of the Ataxia Telangiectasia (AT) pipeline products from the pre-clinical developmental phase to the marketed phase. In the report, a detailed description of the drug is proffered including mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Ataxia Telangiectasia (AT) collaborations, licensing, mergers and acquisition, ...
TY - JOUR. T1 - Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. AU - Degan, Paolo. AU - dIschia, Marco. AU - Pallardó, Federico V.. AU - Zatterale, Adriana. AU - Brusco, Alfredo. AU - Calzone, Rita. AU - Cavalieri, Simona. AU - Kavakli, Kaan. AU - Lloret, Ana. AU - Manini, Paola. AU - Pisanti, Maria Antonietta. AU - Vuttariello, Emilia. AU - Pagano, Giovanni. PY - 2007/6. Y1 - 2007/6. N2 - Objective: To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT). Methods: A set of oxidative stress endpoints were measured in 9 AT homozygotes, 16 AT heterozygotes (parents) and 83 controls (grouped in age ranges as for patients and parents, respectively). The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione (GSSG and GSH); and (c) plasma levels of glyoxal (Glx) and methylglyoxal (MGlx). Results: AT patients displayed a significant decrease in ...
TY - JOUR. T1 - DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection. AU - Lücke-huhle, Christine. AU - Hinrichs, Susanne. AU - Speit, Günter. PY - 1987/12. Y1 - 1987/12. N2 - During selection for methotrexate resistance, SV40-transformed human skin fibroblasts from patients with ataxia telangiectasia (A-T) underwent amplification of the dihydrofolate reductase (DHFR) gene, experienced nearly complete loss of the integrated SV40 sequences and showed a 3.6-fold increase in Ki-ras gene copy number. Over a period of months methotrexate-resistant (MTXr) A-T subclones were obtained, which were able to grow in progressively increasing MTX concentrations up to 100 μM. The ED50 values determined as the effective dose of MTX causing 50% growth inhibition in comparison to control cells increased from 3×10-2 μM for MTXs AT5BI-VA cells to 250 μM MTX for the MTXr AX100 subclone. In contrast, human skin fibroblasts of healthy individuals did ...
TY - JOUR. T1 - Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts. AU - Li, Yuling. AU - Carty, Michael P.. AU - Oakley, Gregory G.. AU - Seidman, Michael M.. AU - Medvedovic, Mario. AU - Dixon, Kathleen. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Ataxia telangiectasia (A-T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses. The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM may play a role similar to that of DNA-PKcs in DSB repair ...
TY - JOUR. T1 - ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. AU - Sasaki, Tomonari. AU - Tian, Huaize. AU - Kukita, Yoji. AU - Inazuka, Masakazu. AU - Tahira, Tomoko. AU - Imai, Takashi. AU - Yamauchi, Masatake. AU - Saito, Toshiyuki. AU - Hori, Tada Aki. AU - Hashimoto-Tamaoki, Tomoko. AU - Komatsu, Kenshi. AU - Nikaido, Osamu. AU - Hayashi, Kenshi. PY - 1998/1/1. Y1 - 1998/1/1. N2 - ATM has been identified as a gene that is responsible for ataxia telangiectasia (AT), a pleiotropic disorder of autosomal recessive inheritance. While many mutations of this gene in AT patients of various ethnicities have been reported, data on Japanese patients are scarce. In this report, we present the results of a thorough survey of ATM mutations in 14 unrelated AT patients, with an emphasis on Japanese subjects. We used a hierarchical strategy in which we extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by ...
Ataxia Telangiectasia & Immunoglobulin M Decreased Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Ravi, Srimadhavi; Barui, Sugata and Kirubakaran, Sivapriya, Targeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancer, in the 68th Gordon Research Conference for Natural Products and Bioactive Compounds, Proctor Academy, Andover, NH, US, Jul. 28- Aug. 2, 2019 ...
BACKGROUND: ATR is a critical regulator of the homologous recombination DNA repair pathway and the cellular response to replication stress. Inhibition of ATR is predicted to selectively enhance the sensitivity of tumor cells, in which DNA repair is often compromised, to standard of care DNA damaging agents, while relatively sparing non-tumor cells which have DNA repair mechanisms to compensate for the loss of ATR. VX-970 is a potent and selective inhibitor of ATR with a Ki | 0.2 nM and intracellular IC50 of 19 nM. RESULTS: VX-970 substantially increases the cytotoxic activity of multiple DNA damaging agents in a broad panel of tumor cell lines, with minimal increase in non-tumor cell cytotoxicity. VX-970 markedly synergizes with cytotoxic agents in mouse xenograft models of several tumor types. At concentrations of VX-970 which inhibit tumor growth, phosphorylation of the downstream biomarker, Chk1, is observed, as is up-modulation of markers of unrepaired double strand DNA breaks, including gamma-H2AX.
The ability to maintain genomic integrity prevents unrestricted cell proliferation and the progression of cancer. DNA repair pathways such as the DNA double-strand break (DSB) response are essential in maintaining this integrity. This system requires activation of the serine/threonine kinase ataxia telangiectasia mutated (ATM) through acetylation by TIP60, a histone acetyl transferase, and subsequent ATM autophosphorylation. During DNA repair, activated ATM phosphorylates the histone variant H2AX several kilobases either side of the break site. This phosphorylation acts a signal for additional repair proteins and chromatin remodeling complexes which repairs DNA. In a previous study, H2AX phosphorylation was induced through the over expression of TIP60 or the SWI3-ADA2-N-CoR-TFIIIB (SANT) domain of p400. It was hypothesised that over expressed TIP60 or SANT domain was able to sequester a putative negative regulator from the ATM-TIP60 complex and artificially induce activation. This study aimed to ...
Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by clinical manifestations that include progressive cerebellar ataxia, neuronal degeneration, hypersensitivity to ionizing radiation (IR), premature aging, hypogonadism, growth retardation, immune deficiency, and an increased risk for cancer (1). The gene mutated in A-T, ATM (ataxia telangiectasia-mutated), encodes a 370-kD protein that is a member of a family of proteins related to phosphatidylinositol 3-kinase (PI-3-K) that have either lipid or protein kinase activity. The subset of this family with the greatest identity to ATM functions in DNA repair, DNA recombination, and cell-cycle control (2, 3). Cell lines derived from A-T patients exhibit hypersensitivity to IR and defects in several IR-inducible cell-cycle checkpoints, including a diminished irradiation-induced arrest in the G1 phase of the cell-cycle mediated by the p53 tumor suppressor gene product (4, 5). In response to DNA damage, cells with wild-type ...
Ataxia Telangiectasia (A-T) - Action for A-T funds high quality peer reviewed medical research to speed up the process of identifying a cure for A-T.
We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity.. ...
A fact sheet about ataxia telangiectasia (A-T), a rare, recessive genetic disorder of childhood that occurs in between one out of 40,000 and one out of 100,000 persons worldwide.
Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a proteins kinase Igf1 Everolimus that has a significant function in the activation of cellular replies to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. for breasts cancers remain unresolved. SOLUTIONS TO investigate the function of ATM in BC susceptibility we examined 76 uncommon sequence variations in the ATM gene within a case-control family members research of 2 570 situations of breasts cancers and 1 448 handles. The variations had been grouped into three types predicated on their most likely pathogenicity as dependant on in silico evaluation and examined by conditional logistic regression. Most likely pathogenic sequence variations had been genotyped in 129 family of 27 carrier probands (15 which transported c.7271T > G) and improved segregation analysis was utilized to estimation the BC penetrance connected with these uncommon ...
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Ataxia Telangiectasia is a progressive degenerative disease which affects various systems of the body. First signs of the disease usually appear during the second year of life.
Cellular response to DNA damage is critical to maintain genomic stability. When a double-strand break (DSB) occurs, the cell activates its checkpoint machinery to halt cell cycle progression and allow proper DSB repair (1). Without such response and repair, the cell will eventually undergo apoptosis or pass on its altered DNA to daughter cells. Checkpoints are enabled through sensing DNA damage, transducing damage signals, and activating effectors. Mechanisms by which DNA damage signals are initiated have begun to be revealed (1, 2) . PI-3-like kinases, including ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), and DNA-PK are believed to play central roles (3). ATM is mutated (lost or inactivated) in the human genetic disorder ataxia-telangiectasia and could be the primary kinase responsible for DSB signaling transduction. Structural chromatin changes activate ATM, which then phosphorylates itself (4). Activated, autophosphorylated ATM in turn phosphorylates the checkpoint ...
Synonyms for Ataxia-telangiectasia in Free Thesaurus. Antonyms for Ataxia-telangiectasia. 3 synonyms for ataxia: ataxy, dyssynergia, motor ataxia. What are synonyms for Ataxia-telangiectasia?
Cells avoid the disastrous effects of DNA damage by activating a checkpoint mechanism to prevent proliferation of cells that contain damaged DNA. The protein kinase ATM is an important component of this signaling mechanism, but precisely how its activity is regulated has not been clear. The protein Nbs1, which is mutated in the human disorder Nijmegen breakage syndrome, forms MRN complexes with two other proteins that participate in DNA repair, Mre11 and Rad50 (Mre11-Rad50-Nbs1, hence, MRN). Nbs is also a substrate for ATM. But now, Lee and Paull suggest that the interaction between Nbs1 and ATM is more complicated. MRN complexes directly activate enzymatic activity of ATM, possibly by causing a conformational change in ATM that alters the affinity of the kinase toward its substrates.. J.-H. Lee, T. T. Paull, Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304, 93-96 (2004). [Abstract] [Full Text]. ...
BackgroundAtaxia telangiectasia (A-T) is a common genetically inherited cause of early childhood-onset ataxia. The infrequency of this disease, vast phenotype variation, disorders with features similar to those of A-T, and lack of definite laboratory test, make diagnosis difficult. In addition, there is no rapid reliable laboratory method for identifying A-T heterozygotes, who susceptible to ionizing radiation (IR), atherosclerosis, diabetes, and cancers. We used SMC1pSer966 (pSMC1) in-cell colorimetric ELISA to diagnosis and screen in A-T families.Materials and Methods: With informed consent, 2cc peripheral blood was collected from the 15 A-T patients, their parents, and 24 healthy controls with no family history of malignancy, diabetes, and atherosclerosis. Extracted peripheral blood mononuclear cells (PBMCs) were cultured in poly-L-Lysine treated 96-well plate with density of 70,000 cells per well. SMC1 phosphorylation was evaluated with cell-based ELISA kit 1 hour after 5 Gy IR and the pSMC1data
This is the first out of two pathways which deals with the DNA damage response. It is comprised of two central gene products (ATM and ATR) influenced by different sources of DNA damage (in blue). The two central genes can both be divides into their most important genes. For the ATM pathway these are TP53 and CHEK2, while CHEK1 is most important for the ATR pathway. The goal of this first pathway is to provide an overview of the most important gene products, processes and changes in cell condition elicited by the DNA damage response while keeping it clear and understandable. Also some microRNAs are implemented to visualize the possible effects they can induce. By doing so a better understanding of the role microRNA play in the DNA damage response might arise. All processes take place in the cytoplasm, except when mentioned differently. ...
Artists concept of Launching the cellular DNA-damage response by the ATR-ATRIP complex. (Image by WANG Guoyan and CHEN Lei, USTC). The researchers published the structural information on Dec 1st in Science.. The ATR protein is the apical kinase to cope with the DNA damages and replication stress, said CAI Gang, a professor of life sciences at the University of Science & Technology of China in Hefei, China, and the lead author on the paper. It has long been a central question to determine the activation mechanism of ATR kinase-how it responds to DNA damage and how it is activated.. CAI and his team used electron microscopy to image the Mec1-Ddc2 complex at 3.9 ångströms, which is about eight times the size of a single atom of helium. The complex is found in yeast and is the equivalent of the human ATR protein and its cell-signaling protein partner, ATRIP.. The ATR kinase is one of six proteins responsible for maintaining the health of the cell. When this family of proteins identifies a ...
This is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two central genes can be divides furthermore into their most important genes. In the ATM pathway are the most important genes TP53 and CHEK2 and on the other hand in the ATR pathway is this CHEK1. If it is not mentioned different, the processes take place in the cell cytoplasm. The goal of this first pathway is to give an overview of the most important gene products, processes and changes in the cell condition through the DNA damage response pathway and at the same time to keep it clearly ...
Because of potential chemotherapeutic (sensitization of chemoresistant cells to death; refs. 3, 4) and chemopreventive (skin cancer prevention; ref. 35) implications, ATR pathway inhibitors have long been sought. Caffeine has been widely used as an ATM/ATR inhibitor, but caffeine requires millimolar levels to inhibit ATR and has several other targets (12, 36). Previous attempts to discover novel DNA damage response inhibitors have focused on finding better ATP-competitive inhibitors of kinases in this pathway. In the present study, we used a phenotype-based screening approach to identify ATR pathway inhibitors, potentially mechanistically distinct from typical ATP-competitive kinase inhibitors. Because the ATR activation mechanism is complex and requires multiple proteins to be recruited to damaged DNA, any of these components of the ATR pathway could potentially be a target of the identified small-molecule inhibitors. Specifically, unlike traditional biochemical screening, this phenotype-based ...
ATM Kinase Inhibitor - CAS 587871-26-9 - Calbiochem ATM Kinase Inhibitor, CAS 587871-26-9, is a cell-permeable, potent, ATP-competitive inhibitor of ATM Kinase (IC₅₀ = 13 nM; Ki = 2.2 nM). - Find MSDS or SDS, a COA, data sheets and more information.
In this issue of Clinical Cancer Research, Saiya-Cork and colleagues used integrative genomic profiling to identify that the insulin receptor (INSR) is significantly overexpressed in about 25% of chronic lymphocytic leukemias (CLL), many of which carry deletion 11q (1). Deletion 11q has been associated with marked lymphadenopathy and rapid disease progression in CLL, leading to short overall survival (2, 3). At diagnosis or initiation of first therapy, deletion 11q is the most common high-risk abnormality in CLL. Although the molecular pathogenesis of CLL with each characteristic chromosome abnormality is being intensively studied, much remains to be understood. Most interest in 11q deletion has focused on loss of the ataxia telangiectasia mutated (ATM) gene, a well-known tumor suppressor gene involved in cell cycle checkpoint signaling and DNA repair. Because 11q deletion generally only affects one of the two chromosomes, the other ATM allele would be expected to be mutated if ATM is a key ...
DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signalling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans.
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The UV broken foci showed the specific phosphorylation of H2AX, a recognized molecular marker of damage reaction initiation. ATR and ATM are main kinases which phosphorylate H2AX upon DNA damage. Pemirolast BMY 26517 The company localization of _H2AX with CPD and 6 4PP has been used to show the involvement of ATR to the UV damage site. Consequently, our data revealed a clear contribution of ATR and ATM kinases in response to UV damage. To examine if ATR and ATM signal transduction can also be working in reaction to 6 4PP, we established the company localization of pATM and _H2AX with 6 4PP at the UV damage sites. The 6 4PP also corp localized with pATM and _H2AX, showing that the ATR/ATM signal transduction is also working in reaction to 6 4PP, and not specific to CPD. More to the point, we showed that ATR and ATM localize to damage sites in G1 arrested cells. This information further supports the involvement of ATR and ATM kinases in response to UV damage, which can be clearly independent of ...
Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative...
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Ceralasertib is a potent and selective ATP competitive inhibitor of ataxia telangiectasia and Rad3 related (ATR) in clinical development as monotherapy and in combination with olaparib (Lynparza) and durvalumab (Imfinzi) in patients with advanced solid tumors. Paired pre- and on-treatment tumour samples from seven patients during ceralasertib monotherapy in Phase 1 studies (NCT02223923, NCT02264678), all ATM expressing, showed increases in pRAD50 on treatment. This study aimed to robustly understand the relationship between ceralasertib pharmacokinetics, pRAD50 (pSer635) induction by immunohistochemistry and anti-tumor efficacy, in mouse xenografted models; to enable interpretation of paired clinical tumour samples. First, in vivo data were generated in a range of xenografted models (HBCx9 [TNBC, Xentech], HCC1806 [BC], OCI-Ly19 [DLBCL] and OE21 [HNSCC]) and NSCLC and HNSCC PDX models at Champions). Mouse ceralasertib doses (6.25 - 25mg/kg BID and 50mg/kg QD) reflected the observed free drug ...
14-3-3 tau mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. 14-3-3 tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage ...
Sigma-Aldrich offers abstracts and full-text articles by [Kenta Yamamoto, Jiguang Wang, Lisa Sprinzen, Jun Xu, Christopher J Haddock, Chen Li, Brian J Lee, Denis G Loredan, Wenxia Jiang, Alessandro Vindigni, Dong Wang, Raul Rabadan, Shan Zha].
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Such an assay has many obvious potential uses, Kastan said, including the assessment of exposure to dangerous agents in the environment. Another potential clinical benefit of these discoveries applies to cancer prevention. Since damage to the DNA appears to contribute to the vast majority of human cancers, enhancing the response of cells to DNA damage could reduce cancer development, Kastan noted. Therefore, the discovery of how ATM is activated could help guide the development of ways to improve cellular responses to DNA damage, including responses to oxidative stress that are either induced or natural ...
Recent efforts to understand the biochemical basis for ATR activation at stalled DNA replication forks have led to new insight into how ATR is regulated and how ATR in turn regulates a network of downstream signaling molecules (9). The seminal observation by Reinhardt and colleagues that loss of p53 function, which occurs in approximately 50% of all cancers, functionally rewires the pathways downstream of ATR underscores the complexity of these survival pathways (7). A detailed understanding of how these pathways are activated by specific therapeutic agents is needed to formulate combinatorial strategies that can successfully create and exploit survival defects. Our study shows, from a genetic standpoint, that not all prospective molecular targets are equivalent, even though they may function in a common pathway. Genetic inhibition of ATR and Cdk2 showed distinct effects from the genetic or pharmacologic inhibition of Chk1 (Figs. 1B, 5B, and 6A).. The HCT116 and DLD-1 cell lines harbor ...
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We envisage the time when customers of any mobile operator will be able to top up their airtime at any UK ATM, said Nigel Wright, operations and development director at Link. This deal paves the way for members of the Link network to offer the services at their ATMs ...
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Ataxia telangiectasia mutated kinase (ATM kinase)[edit]. ATM kinase, a member of the PI3-like family of serine/threonine ... a b c d e f g h i j k l m Petsko, GA and Ringe, D 2009, 'Protein Structure and Function', Oxford University Press Inc., New ... It exerts its effect by phosphorylating target proteins such as P53, MDM2 and chk2. Activation of ATM is facilitated by ... This receptor is a protein with an (αβ)2 quaternary structure. The two large α-subunits are extracellular, while the smaller β- ...
... has been shown to interact with: Ataxia telangiectasia and Rad3 related, Ataxia telangiectasia mutated, HUS1, NHP2L1, ... Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene. The protein encoded by this gene ... This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. This protein recruits the ... Rauen M, Burtelow MA, Dufault VM, Karnitz LM (2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins ...
Alpha-synuclein activates ATM (ataxia-telangiectasia mutated), a major DNA damage repair signaling kinase. Alpha-synuclein ... that heat-shock proteins, which assist in refolding proteins susceptible to aggregation, beneficially affect PD when ... The protein alpha-synuclein has increased presence in the brains of Parkinson's Disease patients and, as α-synuclein is ... Protein aggregates or cytokines from neuroinflammation may interfere with cell receptors and alter their function in the BBB. ...
... protein and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint ... BRCA1-associated ATM activator 1 is a protein in humans that is encoded by the BRAT1 gene. The protein encoded by this ... The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. GRCh38: ... to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein ...
It is composed of ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), DNA-dependent protein ... Many of these functions relate to the ability of class I PI3Ks to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/ ... The class IA PI3K p110α is mutated in many cancers. Many of these mutations cause the kinase to be more active. It is the ... Many other proteins have been identified that are regulated by PtdIns(3,4,5)P3, including Bruton's tyrosine kinase (BTK), ...
Ataxia telangiectasia mutated, BARD1, BRCA1, BRCA2, BRCC3, BRE, Bloom syndrome protein, DMC1, RAD54, P53 RAD52, RAD54B, and ... This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2 and RAD52. The structural basis for Rad51 filament ... Seitz EM, Brockman JP, Sandler SJ, Clark AJ, Kowalczykowski SC (May 1998). "RadA protein is an archaeal RecA protein homolog ... "Analysis of murine Brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals ...
Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related), and the microtubule-binding protein XMAP215/ ... a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" is an acronym for four proteins in ... DNA-dependent protein kinase) Fanconi anemia responsible protein FANCF (FANCF) Damaged DNA-binding protein AlkD (Alkylpurin DNA ... The nuclear transport protein importin beta contains 19 HEAT repeats. Representative examples of HEAT repeat proteins include ...
Ataxia telangiectasia mutated (ATM) Ataxia telangiectasia and Rad3 related (ATR) 5' AMP-activated protein kinase (AMPK) RAF ... 5' adenosine-monophospate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. AMPK is a protein ... The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. Also present ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ...
... apolipoprotein A-IV ARCN1 encoding protein Archain 1 ASRGL1: encoding enzyme L-asparaginase ATM: ataxia telangiectasia mutated ... encoding protein Uncharacterized protein C11orf16 C11orf49: encoding protein UPF0705 protein C11orf49 C11orf52 encoding protein ... encoding protein Acrosomal protein SP-10 AKIP1: A kinase interacting protein 1 ALKBH3 encoding protein AlkB homolog 3, alpha- ... encoding protein C1q and tumor necrosis factor related protein 5 CAPRIN1: encoding protein, cell cycle associated protein 1 ...
... protein kinase C (PKC), ataxia telangiectasia mutated kinase (ATM), cyclin-dependent kinase 5 (CDK5), and casein kinase 1 (CK1 ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2017-05-07. "Human BLAT ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2017-05-06.. ... The relatively fast rate of change in LENG9 compared to that of other proteins suggests that the gene is adaptive for vital ...
A similar mechanism involves the ataxia telangiectasia mutated (ATM) serine/threonine kinase which is an enzyme involved in the ... The NF- κB proteins interact with IκB inhibitory proteins, but during oxidative stress IκB proteins are degraded in the cell. ... The loss of IκB proteins for NF- κB proteins to bind to results in NF- κB proteins entering the nucleus to bind to specific ... The production of ROS in high quantity in cells results in the degradation of biomolecules such as proteins, DNA, and RNA. In ...
Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved ... In E. coli , the proteins involved are the Mut class proteins: MutS, MutL, and MutH. In most Eukaryotes, the analog for MutS is ... These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins. DNA damage ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating ...
... and ataxia telangiectasia-mutated (ATM) most involved in repairing DSBs to the more versatile Rad3-related (ATR). ATR is ... Proteins such as "damage-up" proteins (DDPs) can promote endogenous DNA lesions by either increasing the amount of reactive ... Next, further protein-protein interactions and posttranslational modifications (PTMs) complete the kinase activation, and a ... These three DDR kinases all recognize damage via protein-protein interactions which localize the kinases to the areas of damage ...
Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ... A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 ... A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. ...
At a DSB, MRE11-RAD50-NBS1 (MRN) protein complex recruits ataxia telangiectasia mutated (ATM) kinase which phosphorylates ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ... HGMA proteins are polypeptides of ~100 amino acid residues characterized by a modular sequence organization. These proteins ... High mobility group A (HMGA) proteins, characterized by an AT-hook, are small, nonhistone, chromatin-associated proteins that ...
Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366. „ ... Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90RSK and PKA but not ... AMPKα1 (PRKAA1; protein kinase, AMP-activated, alpha 1 catalytic subunit). *AMPKα2 (protein kinase, AMP-activated, alpha 2 ... LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein ...
Gatei, M; Zhou B B, Hobson K, Scott S, Young D, Khanna K K (2001). «Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 ... Chen, J (2000). «Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic ... ubiquitin protein ligase binding. • transcription regulatory region DNA binding. • ubiquitin-protein transferase activity. • ... Structural consequences and effects on protein-protein interactions». J. Biol. Chem. 276 (44): 41399-406. PMID 11526114. doi: ...
... the ataxia telangiectasia mutated ATM kinase, and 53BP1. Because Artemis can remove damaged ends from DNA, it has been proposed ... "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011. de Villartay ... "Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated ... Artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene. Artemis is a nuclear protein ...
Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein ... Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Chen J (Sep 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ... "A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome". ...
... has been shown to interact with Mdm2 and Ataxia telangiectasia mutated. Abnormalities in this gene are one of the causes ... "Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in ... "Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits". ... The gene encoding the RRM2B protein is located on chromosome 8, at position 8q23.1. The gene and its products are also known by ...
"Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM". J. Biol. Chem. ... Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. The Bloom ... "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity". J. Biol. ... "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity". J. Biol. ...
... has been shown to interact with: Ataxia telangiectasia mutated, BRCA1, H2AFX, MRE11A, Rad50, and TERF2 GRCh38: Ensembl ... Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the NBN gene. Nibrin is a protein associated with ... The central role is carried out by ataxia telangiectasia mutated (ATM) by activating the DSB signaling cascade, phosphorylating ... ICP8, which is a viral single-strand binding protein, is known to interact with several DNA repair proteins, such as Rad50, ...
In the presence of ionizing radiation (IR), the Smc1 subunit of cohesin is phosphorylated by the ataxia telangiectasia mutated ... This alternative form is composed of core RFC proteins RFC2, RFC3, RFC4, and RFC5, but replaces the RFC1 protein with cohesion ... SMC1ß, REC8 and STAG3 are meiosis specific cohesin proteins. The STAG3 protein is essential for female meiosis and fertility. A ... The cohesin ring is composed of two SMC (structural maintenance of chromosomes) proteins and two additional Scc proteins. ...
December 1999). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like ... By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 ... In this organism the Mre11 protein interacts with the Rad50 protein and appears to have an active role in the repair of DNA ... Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the MRE11 gene. The gene has been designated ...
Alpha-synuclein activates ATM (ataxia telangiectasia mutated), a major DNA damage repair signaling kinase. In addition, alpha- ... At the same time, regimens for PD restrict proteins during breakfast and lunch, allowing protein intake in the evening. PD ... where the brain accumulates a different protein known as the tau protein. Considerable clinical and pathological overlap exists ... Levodopa and proteins use the same transportation system in the intestine and the blood-brain barrier, thereby competing for ...
... a protein), MAPRE2 (Microtubule-associated protein RP/EB, a protein), ATM (Ataxia telangiectasia mutated, a protein kinase), ... TERF1 has been shown to interact with: Abl gene, Ataxia telangiectasia mutated, MAPRE1, NME1, PINX1 SALL1, TINF2, TNKS2, and ... the protein has other functions. These functions include the binding of the protein, facilitation in the activity of protein ... The protein has the ultimate use of functioning as an inhibitor of telomerase, a protein enzyme that assists in the elongation ...
Ataxia telangiectasia mutated (ATM) is a kinase that (similar to mTOR) can phosphorylate KAP1 resulting in the switch from ... KRAB-associated protein-1), is a protein that in humans is encoded by the TRIM28 gene. The protein encoded by this gene ... The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of ... "KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for ...
Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ... Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[5] ... A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 ...
Ataxia telangiectasia mutated (ATM) activates after a larger amount of DSBs is detected at later stages of DNA re-replication. ... Once bound to chromatin the ORC recruits the AAA+ ATPase Cdc6 and the coiled-coil domain protein Cdt1. Cdt1 binding and the ... Ataxia telangiectasia and Rad3 related (ATR) is activated earlier when it detects ssDNA in the earlier phases of DNA re- ... Replication initiation proteins are overexpressed in tissue samples from several types of human cancers and experimental ...
... increased phosphorylation of ataxia telangiectasia mutated (ATM), checkpoint kinase 1 (Chk 1), Chk 2; and reduced cell division ... causing oxidized protein levels to increase. This led researchers to conclude that oxidation of cellular proteins is ... as well as inhibiting pore-destabilizing proteins (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer). The ... The altered protein expression in neurons, controlled in part by ROS-dependent demethylation of CpG sites in gene promoters ...
Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ... There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein,[35] a ... Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type ( ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... protein binding. • ATP binding. • cyclin binding. • cyclin-dependent protein serine/threonine kinase activity. • macromolecular ...
Neuropathy, ataxia, and retinitis pigmentosa. References[edit]. *^ a b c d e f g h i j k l m n o p q "Leigh syndrome". Genetics ... shepherding the subunits of COX together into a functional protein complex. This results in a deficit of COX protein, reducing ... This means that two copies of the mutated gene are required to cause the disease, so two unaffected parents, each of whom ... The most severe forms of the disease, caused by a full deficiency in one of the affected proteins, cause death at a few years ...
This leads to a reduction in DNA repair.[16] Furthermore, mutated proteins are more likely to be degraded than normal WRNp.[11] ... Ataxia telangiectasia. *De Barsy syndrome. *PIBI(D)S syndrome. *BIDS syndrome. *Marfanoid-progeroid-lipodystrophy syndrome ... RecQ protein-like helicases (RECQLs), nucleotide excision repair (NER) proteins, and nuclear envelope proteins LMNA (lamins) ... The Bloom syndrome protein interacts with other proteins, such as topoisomerase IIIα and RMI2,[28][29][30] and suppresses ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein kinase activity. • PDZ domain binding. • SH3 domain binding. • scaffold protein binding. • metal ion binding. • kinase ... protein serine/threonine kinase activity. • GO:0001948 protein binding. • ATP binding. • Rho GTPase binding. ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
"Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of ... The protein produced by the TP53 gene, p53, is involved in cell cycle arrest, DNA repair and apoptosis. Defective p53 may not ... Examples of autosomal recessive cancer syndromes are ataxia telangiectasia, Bloom syndrome, Fanconi anemia, MUTYH-associated ... The cause of this disorder is a mutated APC gene, which is involved in β-catenin regulation. Faulty APC causes β-catenin to ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... This protein-related article is a stub. You can help Wikipedia by expanding it.. *v ... protein binding. • metal ion binding. • oxidoreductase activity. • carboxy-lyase activity. • 3-methyl-2-oxobutanoate ...
... autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene; ... Four genes have each been found to be mutated in the majority of adenocarcinomas: KRAS (in 95% of cases), CDKN2A (also in 95 ... "The human pathology proteome in pancreatic cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 28 September 2017 ... The genes often found mutated in PanNETs are different from those in exocrine pancreatic cancer.[47] For example, KRAS mutation ...
... such as ataxia telangiectasia, BRCA1 inherited breast and ovarian cancer, Nbs1 Nijmegen breakage syndrome, RecQL4 Rothmund- ... tropicalis to probe the function of a protein by observing the results of eliminating the protein's activity.[75][76] For ... The mechanism of action for several genes mutated in human cystic kidney disorders (e.g. nephronophthisis) have been ... Xenopus cell-free extracts for biochemical studies of proteins encoded by human disease genes: A unique advantage of the ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *Mammalian target of rapamycin ... protein kinase C activity. • metal ion binding. • kinase activity. • protein binding. • ATP binding. • protein serine/threonine ... Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein kinase activity. • protein serine/threonine kinase activity. • protein binding. • ATP binding. • magnesium ion binding ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... Microtubule-associated serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MAST1 gene.[5] ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ... signal transduction by protein phosphorylation. • stress-activated protein kinase signaling cascade. • activation of protein ... protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ...
Mutated p53 proteins are typically more stable than wild-type, and can inhibit the activity of the wild-type protein in ... Ataxia telangiectasia. *Nijmegen breakage syndrome. Other. *RecQ helicase *Bloom syndrome. *Werner syndrome ... The tetramerization domain plays a major role in the oligomerization of the p53 protein, which exists as a tetramer.[6] This ... With pH in the low to normal physiological range (up to 7.5), the mutant protein forms normal oligomers and retains its ...
ataxia telangiectasia mutated ATM Different mutations in ATM reduce HRR, SSA or NHEJ [48] leukemia, lymphoma, breast [48][49] ... Table 1. DNA repair proteins that, when deficient, cause features of accelerated aging (segmental progeria). Protein. Pathway. ... "Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of ... Protein Repair pathways affected Cancers with increased risk breast cancer 1 & 2 BRCA1 BRCA2 HRR of double strand breaks and ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *Mammalian target of rapamycin ... protein N-terminus binding. • kinase activity. • protein C-terminus binding. • ATP binding. • transferase activity. • protein ... protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mitogen-activated ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein serine/threonine kinase activity. • ATP binding. • kinase activity. • protein binding. Cellular component. • cell ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.[5][6][7] ...
A single-gene (or monogenic) disorder is the result of a single mutated gene. Over 6000 human diseases are caused by single- ... G protein-coupled receptor. (including hormone). Class A. *TSHR (Congenital hypothyroidism 1) ... TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia). *TGFBR1/TGFBR2 (Loeys-Dietz syndrome) ... Spinocerebellar ataxia type-13. *KCNE1 *Jervell and Lange-Nielsen syndrome. *Long QT syndrome 5 ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... In this way protein dynamics can induce a conformational change in the structure of the protein via long-range allostery. ...
Acute myeloid leukemia in a patient with ataxia-telangiectasia: a case report and review of the literature. „Leukemia". 15 (10 ... Należą do nich fuzje MLL/CBP i MOZ/CBP, które dotyczą koaktywatora transkrypcyjnego CBP (CREB binding protein), oraz MLL/p300 i ... Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS. „Cancer". 118 (22), s. 5550-9, Nov 2012. ... CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein kinase activity. • nucleotide binding. • kinase activity. • protein binding. • RNA polymerase II carboxy-terminal ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ...
For instance two dominant-negative germ line mutations were identified in the Ataxia telangiectasia mutated (ATM) gene which ... an aggregate of multiple copies of the same protein, otherwise known as a homomultimeric protein or homooligomeric protein. In ... For example, in humans the Hb gene locus is responsible for the Beta-chain protein (HBB) that is one of the two globin proteins ... In fact, the first study reporting a mutant protein inhibiting the normal function of a wild-type protein in a mixed multimer ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... Protein kinase C ('PKC'). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... The gene codes for a protein kinase. Human homologs of the AKT8 oncogenic protein were identified in 1987.By 1995 it had been ...
... ataxia telangiectasia, Cockayne syndrome, Parkinson's disease and xeroderma pigmentosum.[17][16] Axonal transport[edit]. Axonal ... Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that ... In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG encodes ... ubiquitin-proteasome: protein ubiquitin along with enzymes is key for the degradation of many proteins that cause ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... protein kinase activity. • cAMP-dependent protein kinase activity. • ADP binding. • AMP-activated protein kinase activity. • ... protein binding. • cAMP-dependent protein kinase regulator activity. • protein kinase binding. • ATP binding. • adenyl ... The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer ...
Protein kinase B *AKT1. *AKT2. *AKT3. *Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR ... Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... In general, protein kinases are classified in two major categories based on their substrate specificity, protein tyrosine ... PIKKs have four domains at the protein level, which distinguish them from other protein kinases. From the N-terminus to the C- ...
Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A.. Goodarzi AA1, Jonnalagadda JC, ... Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J. 2004 Nov 10;23(22):4451- ... Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J. 2004 Nov 10;23(22):4451- ... Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J. 2004 Nov 10;23(22):4451- ...
ataxia telangiectasia mutated. ATR. ataxia telangiectasia mutated and rad3-related. DNA-PK. DNA-dependent protein kinase. DNA- ... DNA-Dependent Protein Kinase and Ataxia Telangiectasia Mutated (ATM) Promote Cell Survival in Response to NK314, a ... DNA-Dependent Protein Kinase and Ataxia Telangiectasia Mutated (ATM) Promote Cell Survival in Response to NK314, a ... DNA-Dependent Protein Kinase and Ataxia Telangiectasia Mutated (ATM) Promote Cell Survival in Response to NK314, a ...
2 protein kinases and p53. Caffeine has been widely used to study ATM and ATR signaling because it inhibits these kinases in ... The ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) kinases regulate cell cycle checkpoints by ... The ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) kinases regulate cell cycle checkpoints by ... Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related ( ...
Ataxia telangiectasia-mutated protein can regulate p53 and neuronal death independent of Chk2 in response to DNA damage. J Biol ... The primary transducer of genotoxic stress caused by IR is the nuclear protein kinase ataxia telangiectasia mutated (ATM; refs ... Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci U S A 2000; 97: 10389-94. ... ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation. J Biol Chem 2003; 278: 9309-17. ...
Ataxia telangiectasia mutated kinase (ATM kinase)[edit]. ATM kinase, a member of the PI3-like family of serine/threonine ... a b c d e f g h i j k l m Petsko, GA and Ringe, D 2009, Protein Structure and Function, Oxford University Press Inc., New ... It exerts its effect by phosphorylating target proteins such as P53, MDM2 and chk2. Activation of ATM is facilitated by ... This receptor is a protein with an (αβ)2 quaternary structure. The two large α-subunits are extracellular, while the smaller β- ...
mitogen-activated protein;. ATM,. ataxia telangiectasia mutated. *Accepted December 10, 1997.. *Copyright © 1998, The National ... the in vivo rapamycin-sensitive target and a member of the ataxia telangiectasia mutated (ATM)-related family of kinases that ... To obtain such a protein, we purified recombinant p70S6k fusion proteins from HEK293 cells that had been treated with rapamycin ... including the ribosomal S6 protein and its specific kinase, p70S6k (8, 9); the eIF-4E binding proteins, 4E-BP1 (6, 7) and 4E- ...
The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps ... ataxia telangiectasia mutated (includes complementation groups A, C and D). *ataxia telangiectasia mutated protein ... Ataxia-telangiectasia. Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. ... Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. Cancer Lett. ...
Associate protein substrate. ATM. Ataxia telangiectasia mutated. BAD. Bcl-2-associated death promoter ... Shahrabani-Gargir L, Pandita TK, Werner H. Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor ... Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. ... FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab. 2005;16(4):183-9. doi: 10.1016/j.tem.2005.03.010. ...
The DNA Damage Response Kinases DNA-dependent Protein Kinase (DNA-PK) and Ataxia Telangiectasia Mutated (ATM) Are Stimulated by ... ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related), and the RFC (replication factor C)-like checkpoint protein ... ataxia telangiectasia mutated; ATR, ATM- and Rad3-related; MSH, MutS homolog; ATRIP, ATR-interacting protein; SMC, structure ... binding Protein 1 (TopBP1) and Claspin to DNA Activates Ataxia-Telangiectasia Mutated and RAD3-related (ATR) Phosphorylation of ...
Green Fluorescent Proteins * Luciferases * Ataxia Telangiectasia Mutated Proteins * Protein Phosphatase 2 * 3,3- ... DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage ( ... Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In ...
Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia ... telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates a … ... the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases ...
We demonstrated that ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins directly ... Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) ...
ATM indicates ataxia-telangiectasia mutated gene; NSCLC, non-small cell lung cancer; TP53, tumor protein p53 gene; and crosses ... ATM indicates ataxia-telangiectasia mutated gene; NSCLC, non-small cell lung cancer; TP53, tumor protein p53 gene; and crosses ... ATM indicates ataxia-telangiectasia mutated gene; NGS, next-generation sequencing; and TP53, tumor protein p53 gene. ... Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and ...
Ataxia-telangiectasia mutated (ATM) is a Ser/Thr protein kinase that plays a critical role in DNA damage-induced signaling and ... Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and ATM protein loss in primary gastric cancer ... Mutation at Intronic Repeats of the Ataxia-Telangiectasia Mutated (ATM) Gene and ATM Protein Loss in Primary Gastric Cancer ... Mutation at Intronic Repeats of the Ataxia-Telangiectasia Mutated (ATM) Gene and ATM Protein Loss in Primary Gastric Cancer ...
Leave a Comment / The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM ... The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by ... The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by ... The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by ...
ataxia telangiectasia mutated. AMPK. AMP (Adenosine monophosphate)-activated protein kinase. DDR. DNA damage response ... Protein concentration was measured by Pierce™ BCA Protein Assay Kit. Equal amounts of protein lysates (21 µg/lane) were ... G2M cell cycle checkpoint proteins: Cyclin B1, Cdc2 and p-Cdc2Tyr15. DNA damage response protein: p-H2AXSer139. Signal ... Additionally, it was shown before that ATP-binding cassette proteins are involved in cisplatin resistance [42]. Thus, further ...
AMPK, AMP-kinase; AP1, activator protein 1; APC, antigen-presenting cells; ATM, ataxia-telangiectasia mutated; ATR, ATM- and ... death-associated protein kinase; DDB, damage specific DNA binding proteins 1 and 2; DNA-PK, DNA-dependent protein kinase; DRAM ... 2012). Mitochondrial dysfunction in ataxia-telangiectasia. Blood 119, 1490-1500. doi: 10.1182/blood-2011-08-373639 ... ataxia-telangiectasia (AT), or Cockayne syndrome (CS) patients lead to defective mitophagy and the accumulation of ...
May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. ... Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic ... Serine-protein kinase ATM (EC:2.7.11.1). Alternative name(s):. Ataxia telangiectasia mutated homolog. Short name: ... Protein-protein interaction databases. STRING: functional protein association networks. More...STRINGi. 9823.ENSSSCP00000019250 ...
APCs, antigen-presenting cells; ATM, ataxia telangiectasia mutated; CTL, cytotoxic lymphocytes; DAMP, damage-associated ... a stress-response protein with a role in binding defective proteins and presenting them on the surface of cells. When exposed ... subsequent activation of stress-response pathways through activation of the DNA damage pathway ataxia telangiectasia mutated ( ... high-mobility group box 1 protein; HSP, heat shock proteins; ICAM, intracellular adhesion molecule; IFN-γ, interferon-gamma; IL ...
Ewing sarcoma protein; ATM, ataxia telangiectasia mutated protein; CPSF, cleavage and polyadenylation specificity factor; TLS, ... ataxia telangiectasia (ATM), protein kinase N β, FLASH homolog RIP25, phosphatidylinositol-4-phosphate 3-kinase, and NOXO1. CAS ... Arginine methylation has been shown to regulate protein-protein interactions (29). The discovery that Sm proteins are ... Arginine methylation may regulate the signaling of DNA damage, protein-protein interactions, or protein localization during DNA ...
ataxia telangiectasia mutated protein. ATR. ataxia telangiectasia and Rad3 related protein. BAX. BCL2-associated X protein. ... and immunoblotting analyses indicated expression of proteins related to the unfolded protein response, a major cellular ... 1999 Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins. Nature 399, 708-712. (doi:10.1038/21460) ... d(GpG) intrastrand cisplatin adduct complexed with the high mobility group box protein HMGB1 was solved [21] as was the ...
... tumor protein p53; SMAD4, SMAD family member 4; ATM, ataxia telangiectasia mutated; IDH1, isocitrate dehydrogenase 1 (NADP+); ... STK11 acts by phosphorylating the T-loop of AMPK family proteins, upregulating their activity.. Molecular pathology. Defects in ... A gene on chromosome 19p13.3 that encodes a ubiquitously expressed serine/threonine-protein kinase which controls the activity ... of AMP-activated protein kinase (AMPK) family members, playing a role in various cellular processes such as cell metabolism, ...
1] Ataxia Telangiectasia and Rad3-related protein kinase. [2] Ataxia Telangiectasia Mutated ... ATR[1] is an important signalling protein in DNA double strand break repair and replication stress. Through inhibition of ATR, ... High levels of ATM mutations and protein loss have been characterised across many different tumour types, creating a ...
... ataxia telangiectasia mutated; LYP, lymphoid-specific tyrosine phosphatase; TC-PTP, T cell protein tyrosine phosphatase; STAT5 ... which causes insufficient activation of ataxia telangiectasia mutated (ATM), leading to biased differentiation of CD4 T cells ... This protein is exclusively expressed in cells of the immune system and in T cells negatively regulates TCR signalling by ... Alterations in gen/protein expression or activity found in CD4 T cells from RA patients and their phenotype. ...
... ataxia telangiectasia mutated; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog deleted from ... nutrient-regulated protein kinase, and the IFN-induced, double-stranded RNA-activated protein kinase (PKR; Ref. 23). ... Ataxia-telangiectasia: structural diversity of untranslated sequences suggests complex post-transcriptional regulation of ATM ... A highly conserved family of Y-box proteins is found in cytoplasmic messenger ribonucleoprotein particles, where the proteins ...
Ataxia Telangiectasia Mutated Proteins. *Genetic Variation. *Genetic Association Studies. *Hereditary Nonpolyposis Colorectal ... calcium-binding proteins, G-proteins, oncofetal proteins) in relation to tumor differentiation were detected using gene- ... Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/- ... Furthermore, LJ12 induced tumor cell apoptosis and the protein expression of B cell lymphoma‑2‑associated X protein, caspase‑3 ...
DNA-dependent protein kinase; ATM, ataxia telangiectasia-mutated; ATR, ATM-Rad3-related protein; MDM2, murine double minute 2; ... Chen N., Ma W. Y., Huang C., Dong Z. Translocation of protein kinase Cε and protein kinase Cδ to membrane is required for ... 3 The abbreviations used are: MAP, mitogen-activated protein; ERK, extracellular-signal-regulated protein kinase; JNK, c-Jun NH ... The lysates containing 500 μg of protein were immunoprecipitated using monoclonal mouse IgG against p53 antibody and protein A/ ...
Del11q22.3 ataxia telangiectasia mutated (ATM) as detected by FISH. *Complex karyotype (,= 3 cytogenetic abnormalities on ... Del17p13.1(tumor protein p53 [TP53]) as detected by fluorescence in-situ hybridization (FISH) ... Zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) gene promoter hypomethylation , 20% ...
B, similar protein expression in wild-type and ATM−/− cells following camptothecin treatment. Wild-type (lanes 1-6) or ATM−/− ( ... Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and - ... Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and - ... Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and - ...
In ataxia telangiectasia mutated (Atm)-deficient (Atm−/−) mice, ROS levels were elevated in chondrocytes of growth plates, ... Phosphorylated ATM, the active form of the protein, was detected in growth-plate chondrocytes in wild-type mice (Fig. 5 A). ... Ataxia telangiectasia mutated (ATM) functions in oxidative defense, and mice with Atm loss of function show premature aging ... Abbreviations used: ATM, ataxia telangiectasia mutated; DCF-DA, dichlorodihydrofluorescein diacetate; ERK, extracellular signal ...
  • Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases. (semanticscholar.org)
  • The ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) kinases regulate cell cycle checkpoints by phosphorylating multiple substrates including the CHK1 and -2 protein kinases and p53. (semanticscholar.org)
  • The complex of rapamycin with its intracellular receptor, FKBP12, interacts with RAFT1/FRAP/mTOR, the in vivo rapamycin-sensitive target and a member of the ataxia telangiectasia mutated (ATM)-related family of kinases that share homology with the catalytic domain of phosphatidylinositol 3-kinase. (pnas.org)
  • In eukaryotes , this process occurs by the addition of a phosphate group to serine , threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity. (wikipedia.org)
  • [3] The structures of some autophosphorylation complexes are known from crystals of protein kinases in which the phosphorylation site (Ser, Thr, or Tyr) of one monomer in the crystal is sitting in the active site of another monomer of the crystal in a manner similar to known peptide-substrate/kinase structures. (wikipedia.org)
  • In humans, the central checkpoint kinases ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related), and the RFC (replication factor C)-like checkpoint protein Rad17/RFC2-5 complex have been demonstrated to function upstream of the DNA damage response pathway for the activation of the downstream checkpoint kinase Chk1 by phosphorylation ( 3 ). (pnas.org)
  • The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by bulky adduct-containing DNA. (taleffectors.com)
  • Using this cell-free system along with a wide range of pharmacological, genetic, and biochemical approaches, we recognized the DNA damage response kinases DNA -dependent protein kinase ( DNA -PK) and ataxia telangiectasia mutated (ATM) as bulky DNA damage-stimulated kinases that phosphorylate physiologically vital residues on the checkpoint proteins p53, Chk1, and RPA. (taleffectors.com)
  • The binding of these kinases to damaged DNA triggers the recruitment of additional proteins, many of which become phosphorylated and activated to further transduce signals that orchestrate DNA replication, cell cycle control, transcription, repair of damage, and/or survival versus death. (frontiersin.org)
  • We found that in a mouse JB6 epidermal cell line, resveratrol activated extracellular-signal-regulated protein kinases (ERKs), c-Jun NH 2 -terminal kinases (JNKs), and p38 kinase and induced serine 15 phosphorylation of p53. (aacrjournals.org)
  • In mammalian cells, MAP 3 kinases represent a family of Ser/Thr protein kinases comprised of three distinct components: ERKs, JNKs, and p38 kinase. (aacrjournals.org)
  • We show that ATM is intimately involved in Sp1 hyperphosphorylation during HSV-1 infection rather than individual HSV-1-encoded protein kinases. (asm.org)
  • DNA-PK also belongs to the PI3 kinase-related serine/threonine protein kinase (PI3KK) family, which also includes ATM and ATR kinases ( 1 ). (jimmunol.org)
  • Thus, DNA strand breaks in cortical neurons induce rapid p53-mediated apoptosis through actions of upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. (scialert.net)
  • D e V irgilio and L oewith 2006 ) that encode large (∼280 kDa) proteins highly conserved throughout evolution that have atypical serine/threonine protein kinase activity, yet are related to phosphatidylinositol 3-kinase protein kinases. (genetics.org)
  • Moreover, we show that IR induces phosphorylation-dependent dissociation of PP2A from ATM and loss of the associated protein phosphatase activity. (nih.gov)
  • Inhibition of PP2A-like protein phosphatase activity induces phosphorylation of ATM at serine 1981. (nih.gov)
  • RAFT1 phosphorylation of 4E-BP1 on Thr-36 and Thr-45 blocks its association with the cap-binding protein, eIF-4E, in vitro , and phosphorylation of Thr-45 seems to be the major regulator of the 4E-BP1-eIF-4E interaction in vivo . (pnas.org)
  • RAFT1 phosphorylates p70 S6k much more effectively than 4E-BP1, and the phosphorylation sites on the two proteins show little homology. (pnas.org)
  • Phosphorylation by p70 S6k of the S6 protein of the small ribosomal subunit permits, through unknown mechanisms, efficient translation of mRNAs containing oligopyrimidine tracts in their 5′ untranslated regions ( 12 , 13 ). (pnas.org)
  • We report that MSH2 (MutS homolog 2) protein interacts with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of chromosome 1). (pnas.org)
  • We found that phosphorylation of Chk1 by ATR also requires checkpoint proteins Rad17 and replication protein A. In contrast, phosphorylation of SMC1 by ATR is independent of Rad17 and replication protein A, suggesting that the signaling pathway leading to SMC1 phosphorylation is distinct from that mediated by the checkpoint proteins. (pnas.org)
  • We found that MSH2 protein interacts with the ATR kinase constitutively to form a signaling module that regulates the phosphorylation of downstream effectors including Chk1 and SMC1 (structure maintenance of chromosome 1). (pnas.org)
  • We previously showed that hematopoietic stem cell function was suppressed through elevation of ROS levels, p38 mitogen- activated protein kinase (MAPK) phosphorylation, and p16 INK4A expression in ATM-deficient mice ( 14 ). (rupress.org)
  • Consistent with reports that the DNA damage checkpoint kinase Ataxia Telangiectasia Mutated (ATM) is activated by oxidative stress, ATM phosphorylation was induced in the livers of wild type mice following high fat diet feeding. (biomedsearch.com)
  • Protein phosphorylation and the balance between kinase and phosphatase activity in myocardial ischaemia-reperfusion injury. (sun.ac.za)
  • For mitotic entry to occur, the Cdc25 family of phosphatases dephosphorylates Y15, rapidly activating Cdc2 to enable phosphorylation of proteins that promote mitosis. (genetics.org)
  • We use several methods to show that human lymphoblastoid cells with mutated MSH6 are unable to mount a robust apoptotic response upon treatment with low doses of alkylator, that mutations in MSH6 impair the proper phosphorylation of threonine 68 on Chk2, and also that p53 Serine 20 phosphorylation (but not Serine 15 phosphorylation) is almost completely abrogated in these mutant cells. (ufl.edu)
  • p53 phosphorylation is mediated by ataxia telangiectasia mutated (ATM) kinase. (scialert.net)
  • NVP-BEZ235 abrogated the radiation-induced phosphorylation of both DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated. (aspetjournals.org)
  • Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase. (pubfacts.com)
  • Serines 317 and 345 were identified as sites of phosphorylation in vivo, and ATR (the ATM- and Rad3-related protein kinase) phosphorylated both of these sites in vitro. (asm.org)
  • These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo. (sciencemag.org)
  • IR induces rapid, de novo phosphorylation of endogenous p53 at two serine residues within the first 24 amino acids of the protein, one of which was identified as Ser 15 ( 7 , 8 ). (sciencemag.org)
  • Phosphorylation of p53 at Ser 15 in response to DNA damage correlates with both the accumulation of total p53 protein as well as with the ability of p53 to transactivate downstream target genes in wild-type cells ( 8 ). (sciencemag.org)
  • A gene on chromosome 19p13.3 that encodes a ubiquitously expressed serine/threonine-protein kinase which controls the activity of AMP-activated protein kinase (AMPK) family members, playing a role in various cellular processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. (thefreedictionary.com)
  • The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing doublestrand breaks. (acronymfinder.com)
  • FRDA is most often caused by a homozygous GAA repeat expansion mutation (typically between 600 and 1200 repeats) in the first intron of the frataxin gene (FXN), which is found on chromosome 9q21.11 and encodes the protein frataxin 2 , 9 . (nature.com)
  • Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) encodes the p110α subunit of the mitogenic signaling protein phosphoinositide 3-kinase (PI3K). (humpath.com)
  • This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. (genecards.org)
  • The budding yeast Saccharomyces cerevisiae encodes an ortholog of the Bloom syndrome (BLM) protein that is designated Sgs1 (Small growth suppressor 1). (wikipedia.org)
  • We identified a mutation in tra1 , which encodes one of two homologs of transformation/transcription domain-associated protein (TRRAP), an ATM/R-related pseudokinase that scaffolds several histone acetyltransferase (HAT) complexes. (genetics.org)
  • ATM encodes a protein that is involved in DNA damage repair. (rareshare.org)
  • AT is caused by mutations in the ATM gene which encodes a protein with the same name. (rareshare.org)
  • The gene mutated in A-T, ATM (ataxia telangiectasia-mutated), encodes a 370-kD protein that is a member of a family of proteins related to phosphatidylinositol 3-kinase (PI-3-K) that have either lipid or protein kinase activity. (sciencemag.org)
  • Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. (medlineplus.gov)
  • Most of these mutations disrupt protein production, resulting in an abnormally small, nonfunctional version of the ATM protein. (medlineplus.gov)
  • Instead of activating DNA repair, the defective ATM protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (medlineplus.gov)
  • The mutations causing A-T completely inactivate or eliminate the ATM protein. (nih.gov)
  • We hypothesized that ATM gene intron mutations targeted by microsatellite instability (MSI) cause ATM protein loss in a subset of GC. (cdc.gov)
  • Two human GC cell lines (SNU-1 and -638) showed ATM intron mutations, deletion in RT-PCR and direct sequencing, and ATM protein loss by IHC. (cdc.gov)
  • High levels of ATM mutations and protein loss have been characterised across many different tumour types, creating a significant opportunity for ATR inhibitors clinically. (pharmiweb.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. (abnova.com)
  • The analysis of two tandem mass spectra for each methyl-specific antibody resulted in the identification of over 200 new proteins that are putatively arginine-methylated. (mcponline.org)
  • By Western blot this antibody detects a ~370 kDa protein representing the phospho-ATM kinase in crude lysates from gamma irradiated HeLa cells. (fishersci.com)
  • We demonstrated that ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins directly phosphorylate Dbf4 in response to ionizing radiation and replication stress. (scripps.edu)
  • ATR together with Rad3-related acronyms for a checkpoint kinase that is homologous to the ataxia telangiectasia mutated protein mutated in Ataxia telangiectasia and the yeast RAD3 kinase is presented. (ebscohost.com)
  • We demonstrate that the ataxia telangiectasia and Rad3 related (ATR)-mediated S phase checkpoint acts as a surveillance mechanism to prevent rereplication. (rupress.org)
  • Maladaptive proximal tubule (PT) repair has been implicated in kidney fibrosis through induction of cell-cycle arrest at G2/M. We explored the relative importance of the PT DNA damage response (DDR) in kidney fibrosis by genetically inactivating ataxia telangiectasia and Rad3-related (ATR), which is a sensor and upstream initiator of the DDR. (jci.org)
  • Introduction Ataxia telangiectasia mutated and Rad3 Related (ATR) proteins kinase is an integral sensor of single-stranded DNA connected with stalled replication forks and fix intermediates generated during DNA fix. (bioinf.org)
  • Ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication forks, are two major DDRs processing structurally complicated DNA damage. (pubfacts.com)
  • ATR (the ATM- and Rad3-related protein kinase) also contributes to checkpoint control in eukaryotes ( 13 , 32 ). (asm.org)
  • Ataxia telangiectasia mutated and Rad3 related kinase (ATR) signals replication stress and DNA damage to S and G2 arrest and promotes DNA repair. (mdpi.com)
  • One of the most versatile elements of the DDR is the Ataxia-telangiectasia-mutated and Rad3-related kinase (ATR). (mdpi.com)
  • In support of this, we show that ATM interacts with the scaffolding (A) subunit of protein phosphatase 2A (PP2A), that the scaffolding and catalytic (C) subunits of PP2A interact with ATM in undamaged cells and that immunoprecipitates of ATM from undamaged cells contain PP2A-like protein phosphatase activity. (nih.gov)
  • Clonogenic assays demonstrated a significant sensitization in NK314-treated cells deficient in DNA-dependent protein kinase (DNA-PK) catalytic subunit, Ku80, ataxia telangiectasia mutated (ATM), BRCA2, or XRCC3 compared with wild-type cells, indicating that both nonhomologous end-joining and homologous recombination DNA repair pathways contribute to cell survival. (aspetjournals.org)
  • Initiation factor 4F complexes with these mRNAs through the interaction of its eIF-4G subunit with eIF-4E, the cap-binding protein that recognizes the N 7 -methyl-GpppN structure of the 5′ end of all nonorganellar mRNAs. (pnas.org)
  • The eIF4F translation initiation complex is then formed by the assembly of eIF4E, the RNA helicase eIF4A, and eIF4G, a scaffolding protein that mediates the binding of the 40S ribosomal subunit to the mRNA molecule through interaction with the eIF3 protein present on the 40S ribosome. (aacrjournals.org)
  • The DNA-dependent protein kinase (DNA-PK) is a cNHEJ factor that encompasses the Ku70-Ku80 (KU) heterodimer and the large DNA-PK catalytic subunit (DNA-PKcs). (jimmunol.org)
  • The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. (genecards.org)
  • The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. (genecards.org)
  • Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. (abcam.com)
  • It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency, with defects in both cellular and humoral immunity. (nih.gov)
  • Ataxia-telangiectasia (A-T) [1] is a progressive neurodegenerative disorder characterized by a wide range of clinical manifestations, including cerebellar ataxia, conjunctival telangiectases, recurrent sinopulmonary infections, radiosensitivity, and increased cancer susceptibility (1). (acronymfinder.com)
  • Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by clinical manifestations that include progressive cerebellar ataxia, neuronal degeneration, hypersensitivity to ionizing radiation (IR), premature aging, hypogonadism, growth retardation, immune deficiency, and an increased risk for cancer ( 1 ). (sciencemag.org)
  • These genes encode large proteins containing a phosphatidylinositol 3-kinase domain, some of which have protein kinase activity. (nih.gov)
  • As important genes in the DNA damage response pathway, comutation in the tumor protein p53 (TP53) and ataxia-telangiectasia mutated (ATM) genes may be associated with genomic instability and hypermutation. (cdc.gov)
  • thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. (abnova.com)
  • This mRNA is apparently translated and produces a catalytically active ATM protein that responds to DNA damage by phosphorylating p53 and Chk2. (jneurosci.org)
  • DDR is mediated by a signal transduction cascade involving the ataxia telangiectasia mutated (ATM-) check point kinase 2 (Chk2)-p53 axis [ 8 , 9 ]. (hindawi.com)
  • Furthermore, JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 both could reverse the EA upregulation of the protein of Chk2 level, significantly. (sigmaaldrich.com)
  • Upon exposure to MNNG and crosslinking agents, cells deficient in MMR proteins exhibit impaired G 2 /M cell cycle arrest, reduced activation of the p53/p73 apoptosis pathway, and resistance to the cytotoxicity of these DNA-damaging agents ( 12 - 14 ). (pnas.org)
  • The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease. (biomedsearch.com)
  • Our results unveiled a previously unknown mechanism through which disruption of protein homeostasis induces caspase-8 oligomerization, activation, and apoptosis. (asm.org)
  • In addition, since both the proteasome and autophagolysosome pathways function as a safeguard system to degrade misfolded or unwanted proteins, a failure within either degradation pathway leads to endoplasmic reticulum (ER) stress ( 16 ), which can induce apoptosis through upregulation of the BH3-only proteins Puma and Bim ( 44 , 46 ). (asm.org)
  • The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ago. (nih.gov)
  • Ataxia-telangiectasia is a rare autosomal recessive disorder characterized by progressive neurologic degeneration, immunologic deficiency, and an increased risk of lymphoid cancer. (fishersci.com)
  • A definition of the term "ataxia telangiectasia," which is an autosomal recessive human disorder is presented. (ebscohost.com)
  • Ataxia-telangiectasia (A-T) is a rare degenerative disorder that first becomes apparent during childhood. (atcp.org)
  • The ataxia telangiectasia-mutated (ATM) protein, a member of the related phosphatidylinositol 3-like kinase family encoded by a gene responsible for the human genetic disorder ataxia telangiectasia, regulates cellular responses to DNA damage and viral infection. (asm.org)
  • The ATM gene is mutated in the human genetic disorder ataxia telangiectasia ( 58 ). (asm.org)
  • Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and ATM protein loss in primary gastric cancer with microsatellite ins. (cdc.gov)
  • The frequencies of ATM mutation, MSI, and ATM protein loss were 12.9% (78/604), 9.2% (81/882) and 15.2% (134/839), respectively. (cdc.gov)
  • Analysis of associations among MSI, ATM gene mutation, and ATM protein loss revealed highly co-existing ATM gene alterations and MSI. (cdc.gov)
  • ATM intron mutation and ATM protein loss were detected in 69.3% (52/75) and 53.3% (40/75) of MSI positive GC. (cdc.gov)
  • MSI positivity and ATM protein loss were present in 68.4% (52/76) and 48.7% (37/76) of GC with ATM intron mutation. (cdc.gov)
  • ATM mutation and ATM protein loss had characteristics of old age, distal location of tumor, large tumor size, and histologic intestinal type. (cdc.gov)
  • Our study might be interpreted as that ATM gene mutation at intron might be targeted by MSI and lead to ATM protein loss in a selected group of GC. (cdc.gov)
  • AT occurs due to a mutation in the Ataxia Telangiectasia Mutated (ATM) gene. (rareshare.org)
  • STK11 acts by phosphorylating the T-loop of AMPK family proteins, upregulating their activity. (thefreedictionary.com)
  • also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation. (sigmaaldrich.com)
  • Studies with rapamycin ( 4 ), a potent immunosuppressant, have uncovered a signaling pathway that modulates protein synthesis in yeast ( 5 ) and animal cells ( 6 , 7 ). (pnas.org)
  • Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). (aacrjournals.org)
  • Excess ROS can overwhelm a cell's antioxidant scavenging capacity, causing oxidative damage to DNA, lipids, and proteins, as well as concomitant cellular damage ( 11 ). (rupress.org)
  • Cellular proteins are degraded by two mechanistically connected processes: the ubiquitin-proteasomal pathway and the autophagolysosomal pathway ( 11 , 16 , 32 , 35 ). (asm.org)
  • The protein kinase ATM (ataxia telangiectasia mutated) mediates cellular response to DNA damage induced by radiation. (selleckchem.com)
  • Cryo-EM has enabled researchers to define the world's first protein structures for human ataxia telangiectasia mutated (ATM). (fei.com)
  • ATR senses single-strand DNA breaks and DNA cross-linking and phosphorylates and activates the checkpoint protein Chk1. (jci.org)
  • However, these cells are semi-wee even when overexpressing chk1 + and accumulate inactive Wee1 protein. (genetics.org)
  • Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation. (asm.org)
  • The phosphorylated form of Chk1 possessed higher intrinsic protein kinase activity and eluted more quickly on gel filtration columns. (asm.org)
  • Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. (medlineplus.gov)
  • Changes in the expression or availability of components of the translational machinery and in the activation of translation through signal transduction pathways can lead to more global changes, such as an increase in the overall rate of protein synthesis and translational activation of the mRNA molecules involved in cell growth and proliferation. (aacrjournals.org)
  • Gene expression is quite complicated, however, and is also regulated at the level of mRNA stability, mRNA translation, and protein stability. (aacrjournals.org)
  • Moreover, western blotting and real-time PCR were used to examine the protein expression levels and the mRNA expression levels, respectively. (cancerindex.org)
  • In the present study, we have examined whether DNA-PK activity correlates with radiation sensitivity of 14 esophageal cancer cell lines and whether DNA-PK activity correlates with expression of Ku70, Ku80, or DNA-PKcs protein. (aacrjournals.org)
  • This fusion results in expression of full-length or N-terminally truncated ERG protein in prostate epithelia. (bireme.br)
  • In mouse models, loss of DNA-PKcs ( DNA-PKcs −/− ) abrogates end processing (e.g., hairpin opening), but not end-ligation, whereas expression of the kinase-dead DNA-PKcs protein ( DNA-PKcs KD/KD ) abrogates end-ligation, suggesting a kinase-dependent structural function of DNA-PKcs during cNHEJ. (jimmunol.org)
  • Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. (semanticscholar.org)
  • Cell death protein expression patterns in mouse forebrain are mostly similar to cultured neurons. (scialert.net)
  • Thus, a recombinant, FLAG peptide-tagged, wild-type ATM was used as a source of ATM protein, and a FLAG peptide-tagged, mutant ATM expression construct was generated in which two of the three critical amino acid residues required for catalysis were mutated (Asp 2870 → Ala and Asn 2875 → Lys) ( 13 ). (sciencemag.org)
  • Here, the cell cycle distribution by flow cytometry was examined and the protein expression by the western blotting methods was analyzed. (sigmaaldrich.com)
  • DIAGNOSIS Ataxia-telangiectasia DISCUSSION Ataxia-telangiectasia (AT), also known as Louis-Bar syndrome, is a hereditary autosomal recessive progressive multisystem disease. (acronymfinder.com)
  • Because different DNA-damaging agents generate different DNA lesions, a key question in damage signaling is how the checkpoint proteins recognize different DNA lesions. (pnas.org)
  • Eukaryotic cells activate an evolutionarily conserved set of checkpoint proteins that rapidly induce cell cycle arrest to prevent replication or segregation of damaged DNA before repair is completed. (asm.org)
  • The major protein complexes that were purified include components required for pre-mRNA splicing, polyadenylation, transcription, signal transduction, and cytoskeleton and DNA repair. (mcponline.org)
  • The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. (sciencemag.org)
  • ATM phosphorylates proteins instead of lipid and has many downstream targets that act as cell-cycle regulators including: P53, Mdm2, BRCA1, and SMC1. (fishersci.com)
  • Furthermore, we show that replication protein A 2 and retinoblastoma protein are both downstream targets for ATR that are important for the inhibition of DNA rereplication. (rupress.org)
  • This is defined as the transfer of phosphoryl groups [(PO3)2-] from one molecule to another, and serves as a transfer of energy that results in the activation, or deactivation of downstream proteins. (biolegend.com)
  • Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and Mortality in Patien. (cdc.gov)
  • At BioLegend, we offer a wide array of phospho protein-related products for use in flow cytometry, Western blot, and microscopy applications. (biolegend.com)
  • OA did not induce gamma-H2AX foci, suggesting that it induces ATM autophosphorylation by inactivation of a protein phosphatase rather than by inducing DNA double-strand breaks. (nih.gov)
  • They also provide access to DDR sensors such as the Mre11-Rad50-Nbs1 (MRN) complex which binds double strand breaks (DSBs) and recruits ATM kinase (Figure 1 ) and the replication protein A (RPA) complex which responds predominantly to single strand DNA lesions and recruits ATR kinase. (frontiersin.org)
  • ATR [1] is an important signalling protein in DNA double strand break repair and replication stress. (pharmiweb.com)
  • The MRN complex, comprised of the Mre11, Rad50 and NBS1 proteins, senses DNA damage, known as double-strand breaks, within the cell. (emaxhealth.com)
  • Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. (genecards.org)
  • One mechanism of DNA damage recognition has been elucidated recently, in which binding of replication protein A (RPA) to single-stranded DNA (ssDNA) results in recruitment of the ATR-interacting protein ATRIP to load the ATR/ATRIP complex to ssDNA, leading to activation of ATR ( 4 ). (pnas.org)
  • Once replication is activated by the Cdks and Cdc7/Dbf4 kinase, pre-RCs are disassembled and the reassociation of MCM proteins with origins is not permitted until the completion of mitosis. (rupress.org)
  • We are particularly interested in understanding how DNA damage is identified and resolved during DNA replication, when the genome is particularly vulnerable due to stalling of the replication fork at naturally arising and induced DNA lesions, structures or protein-DNA complexes. (stanford.edu)
  • New Pathways for Genome Stability/Human Disease: Recently, we performed a genome-wide siRNA screen to define the processes and proteins that protect cells from DNA damage, particularly during DNA replication. (stanford.edu)
  • The mismatch repair (MMR) proteins play key roles in postreplicational mispair correction that is essential for genomic stability ( 7 ). (pnas.org)
  • However, the substrate for these processes is not the naked DNA molecule, but chromatin, a highly structured and dynamic macromolecular entity formed by the association of genomic DNA with histones and non-histone proteins. (biomedcentral.com)
  • Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (medlineplus.gov)
  • Research suggests that people who carry one mutated copy of the ATM gene in each cell may have an increased risk of developing several other types of cancer. (medlineplus.gov)
  • Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. (medlineplus.gov)
  • The discovery of the protein A-T mutated (ATM) that is deficient in A-T paved the way for rapid progress on understanding how ATM functions with a host of other proteins to protect against genome instability and reduce the risk of cancer and other pathologies. (nih.gov)
  • We have previously reported the ATM protein loss by immunohistochemistry (IHC) in 16% of human gastric cancer (GC) tissue. (cdc.gov)
  • E) Immunohistochemistry of ATM protein in gastric cancer cell-lines. (cdc.gov)
  • Here we review the basic principles of translational control, the alterations en countered in cancer, and selected therapies targeting translation initiation to elucidate potential new therapeutic avenues. (aacrjournals.org)
  • We investigated the relationship between DNA-dependent protein kinase (DNA-PK) activity and radiation sensitivity using 14 esophageal cancer cell lines, TE 1-14. (aacrjournals.org)
  • Alteration of this gene, along with dramatic downregulation of WWOX protein, is shown in the majority of invasive cancer cells. (humpath.com)
  • Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. (nii.ac.jp)
  • University of Michigan researchers have discovered that a key protein in cells plays a critical role in not one, but two processes affecting the development of cancer. (emaxhealth.com)
  • Most proteins involved in responding to DNA damage that can cause cancer either help detect the damage and warn the rest of the cell, or help repair the damage," says David O. Ferguson, M.D., Ph.D., the study's lead author. (emaxhealth.com)
  • ATM is a key trigger protein in the DNA damage response and a prime therapeutic target in cancer research. (fei.com)
  • Since cancerous cells often display elevated protein synthesis and by-product disposal, inhibition of the protein degradation pathways is an emerging approach for cancer therapy. (asm.org)
  • Cancer cells, owing to their aberrant transcription/translation activity and protein disposal, may become more vulnerable to proteotoxicity. (asm.org)
  • Roles of DNA-dependent protein kinase and ATM in cell-cycle-dependent radiation sensitivity in human cells. (biomedsearch.com)
  • A key component of the DNA damage checkpoint is ATM (ataxia telangiectasia-mutated), a 370-kDa protein kinase ( 58 ). (asm.org)
  • We demonstrate that uncontrolled DNA unwinding by minichromosome maintenance proteins upon Cdt1 overexpression is an important mechanism that leads to ssDNA accumulation and checkpoint activation. (rupress.org)
  • Ataxia-telangiectasia Mutated (ATM) is a protein that belongs to the PI3/PI4 kinase family. (fishersci.com)
  • The protein encoded by this gene belongs to the PI3/PI4-kinase family. (abnova.com)
  • Molecularly, DDR is initiated by the rapid recruitment of several nuclear proteins involved in the repair process to the site of DNA damage to form a complex, which acts to repair DNA damage and promote cell survival. (hindawi.com)
  • AKT, also known as protein kinase B (PKB) or RAS-alpha, is a ubiquitous serine/threonine kinase that plays an important role in diverse biological responses such as regulation of metabolism, cell survival, and growth. (thermofisher.com)
  • The protein also functions in the regulation of the cell cycle in response to DNA damage. (genecards.org)
  • a-synuclein may be involved in the regulation of dopamine release and transport and also may function to induce fibrillization of microtubule-associated protein tau. (biolegend.com)
  • Xu P, LaVallee P, Lin J, Hoidal J. Characterization of proteins binding to E-box/Ku86 sites and function of Ku86 in transcriptional regulation of the human xanthine oxidoreductase gene. (labome.org)
  • The ATM protein has a number of functions, but most importantly, it is involved in the regulation of the cell cycle in response to DNA damage. (rareshare.org)
  • There are possible roles for both ions within the Golgi, including roles in protein modification, in regulation of sorting and vesicular traffic, and in removal of toxic levels of ions. (genetics.org)
  • Moreover, the transcription factor Sp1 was found to bind to this region in response to oxidative stress under the regulation of ataxia telangiectasia mutated (ATM) kinase. (mdpi.com)
  • Friedreich's ataxia is associated with mitochondrial respiratory chain dysfunction, mitochondrial iron accumulation, decreased mitochondrial DNA levels, oxidative stress, reduced generation of ATP and muscular weakness. (nature.com)
  • Furthermore, HCV viral nucleocapsid protein, an HCV core protein, was shown to increase oxidative stress in the liver [ 7 , 8 ]. (mdpi.com)
  • When the MRN complex doesn't work properly, inherited human neurological diseases, such as ataxia-telangiectasia-like syndrome and Nijmegen breakage syndrome, result. (emaxhealth.com)
  • Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. (genecards.org)
  • It has been shown that arginine methylation regulates protein localization ( 2 ). (mcponline.org)
  • Subsequently it was shown that arginine methylation regulates the import of Npl3p ( 24 ) and the protein localization of hnRNP A2 ( 25 ), Sam68 ( 26 ), and p80-coilin ( 27 , 28 ). (mcponline.org)
  • The MA1-2020 immunogen is a phosphorylated synthetic peptide corresponding to the residues S(1974) L A F E E S(p) Q S T T I S S(1988) of human ATM Kinase protein. (fishersci.com)
  • Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. (wikipedia.org)
  • The normal protein may act to suppress inappropriate homologous recombination. (wikipedia.org)
  • Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia mutated protein, ATM. (nii.ac.jp)
  • In response to DNA damage, cells with wild-type ATM accumulate p53 protein and show a subsequent increase in p53 activity, whereas cells with defective ATM show a smaller increase in the amount of p53 protein in response to IR ( 4 , 6 ). (sciencemag.org)
  • Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response. (abcam.com)
  • The most common form of the protein, is the full 140 amino acid-long transcript. (biolegend.com)
  • Ataxia telangiectasia (AT)is a rare genetic disease that is characterized by progressive impairment of voluntary movement coordination (ataxia), formation of thread-like red patterns on the skin by widened blood vessels (telangiectasia), weakened immune system with frequent respiratory infections, sensitivity to radiation, and increased risk of certain malignancies. (rareshare.org)
  • Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. (nih.gov)
  • Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro. (nih.gov)
  • B ) C35ABR cells were incubated for 2 h with increasing concentrations of OA as indicated and processed as described in panel A. ( C ) The extracts shown in panel B were assayed for the percent of PP1 (light bars) or PP2A-like (dark bars) protein phosphatase activity remaining. (nih.gov)
  • Cells were lysed in NETN buffer with or without protein phosphatase inhibitors as indicated. (nih.gov)
  • Increases in the translation of certain mRNAs are an important response to mitogen stimulation ( 1 - 3 ), but little is known about the signaling pathways that link growth stimuli to the activation of the protein synthesis machinery. (pnas.org)
  • Ataxia-telangiectasia mutated (ATM) is a Ser/Thr protein kinase that plays a critical role in DNA damage-induced signaling and initiation of cell cycle checkpoint signaling in response to DNA-damaging agents such as ionizing radiation. (cdc.gov)
  • DNA damage response utilizes proteins involved in sensing, signaling, and repair of DNA damage. (frontiersin.org)
  • Post-translational modifications of histone proteins are involved in repair and DNA damage signalling processes in response to genotoxic stresses. (biochemj.org)
  • Conversely, mutants in the key DNA damage signalling factor ATM (ATAXIA TELANGIECTASIA MUTATED) display increased histone acetylation upon irradiation, linking the DNA damage response with dynamic changes in histone modification in plants. (biochemj.org)
  • Gcn2 was first described in budding yeast as a serine/threonine protein kinase involved in the response to amino acid starvation and this is its best characterized role to date. (biochemsoctrans.org)
  • This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. (abnova.com)
  • The gene that is mutated in ataxia-telangiectasia (A-T), ATM, is catalytically activated in response to DNA damage. (jneurosci.org)
  • This enhanced caspase-8 oligomerization and activation are promoted through its interaction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light chain 3 (LC3), which are enriched at intracellular membranes in response to proteotoxic stress. (asm.org)
  • The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. (sciencemag.org)
  • However, cells with diminished DNA-PK activity still normally accumulate p53 protein and undergo G 1 arrest in response to IR ( 10 ). (sciencemag.org)