Adenovirus E3 Proteins: Proteins transcribed from the E3 region of ADENOVIRUSES but not essential for viral replication. The E3 19K protein mediates adenovirus persistence by reducing the expression of class I major histocompatibility complex antigens on the surface of infected cells.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Apoptosis: 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.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Molecular Sequence Data: 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.Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Death: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.Death, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Brain Death: A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)Fetal Death: Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.Attitude to Death: Conceptual response of the person to the various aspects of death, which are based on individual psychosocial and cultural experience.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Cell Survival: 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.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Signal Transduction: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Line, Tumor: A cell line derived from cultured tumor cells.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.CARD Signaling Adaptor Proteins: A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.Lymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Health Physics: The science concerned with problems of radiation protection relevant to reducing or preventing radiation exposure, and the effects of ionizing radiation on humans and their environment.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Radioactive Waste: Liquid, solid, or gaseous waste resulting from mining of radioactive ore, production of reactor fuel materials, reactor operation, processing of irradiated reactor fuels, and related operations, and from use of radioactive materials in research, industry, and medicine. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Granulosa Cells: Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Anoikis: APOPTOSIS triggered by loss of contact with the EXTRACELLULAR MATRIX.Muridae: A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Asthenozoospermia: A condition in which the percentage of progressively motile sperm is abnormally low. In men, it is defined as Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA.Abstracting and Indexing as Topic: Activities performed to identify concepts and aspects of published information and research reports.Kinetin: A furanyl adenine found in PLANTS and FUNGI. It has plant growth regulation effects.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.Cytokinins: Plant hormones that promote the separation of daughter cells after mitotic division of a parent cell. Frequently they are purine derivatives.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.

Subcellular distribution and redistribution of Bcl-2 family proteins in human leukemia cells undergoing apoptosis. (1/660)

It has been suggested that the ratio of Bcl-2 family proapoptotic proteins to antiapoptotic proteins determines the sensitivity of leukemic cells to apoptosis. However, it is believed that Bcl-2 family proteins exert their function on apoptosis only when they target to the mitochondrial outer membrane. The vinblastine-resistant T-lymphoblastic leukemic cell line CEM/VLB100 has increased sensitivity to tumor necrosis factor-alpha (TNF-alpha)-induced cytochrome c release, mitochondrial respiratory inhibition, and consequently apoptosis, compared with parental CEM cells. However, there was no difference between the two cell lines in the expression of Bcl-2 family proteins Bcl-2, Bcl-XL, Bcl-XS, Bad, and Bax at the whole cell level, as analyzed by Western blotting. Bcl-2 mainly located to mitochondria and light membrane as a membrane-bound protein, whereas Bcl-XL was located in both mitochondria and cytosol. Similar levels of both Bcl-2 and Bcl-XL were present in the resting mitochondria of the two cell lines. Although the proapoptotic proteins Bcl-XS, Bad, and Bax were mainly located in the cytosol, CEM/VLB100 mitochondria expressed higher levels of these proapoptotic proteins. Subcellular redistribution of the Bcl-2 family proteins was detected in a cell-free system by both Western blotting and flow cytometry after exposure to TNF-alpha. The levels of Bcl-2 family proteins were not altered at the whole cell level by TNF-alpha. However, after exposure to TNF-alpha, Bax, Bad, and Bcl-XS translocated from the cytosol to the mitochondria of both cell lines. An increase in Bcl-2 levels was observed in CEM mitochondria, which showed resistance to TNF-alpha-induced cytochrome c release. By contrast, decreased mitochondrial Bcl-2 was observed in CEM/VLB100 cells, which released cytochrome c from the mitochondria and underwent apoptosis as detected by fluorescence microscopy. We conclude that mitochondrial levels of Bcl-2 family proteins may determine the sensitivity of leukemic cells to apoptosis and that, furthermore, these levels may change rapidly after exposure of cells to toxic stimuli.  (+info)

Dissociation of apoptosis from proliferation, protein kinase B activation, and BAD phosphorylation in interleukin-3-mediated phosphoinositide 3-kinase signaling. (2/660)

Interleukin-3 (IL-3) acts as both a growth and survival factor for many hemopoietic cells. IL-3 treatment of responsive cells leads to the rapid and transient activation of Class IA phosphoinositide-3-kinases (PI3Ks) and the serine/threonine kinase Akt/protein kinase B (PKB) and phosphorylation of BAD. Each of these molecules has been implicated in anti-apoptotic signaling in a wide range of cells. Using regulated expression of dominant-negative p85 (Deltap85) in stably transfected IL-3-dependent BaF/3 cells, we have specifically investigated the role of class IA PI3K in IL-3 signaling. The major functional consequence of Deltap85 expression in these cells is a highly reproducible, dramatic reduction in IL-3-induced proliferation. Expression of Deltap85 reduces IL-3-induced PKB phosphorylation and activation and phosphorylation of BAD dramatically, to levels seen in unstimulated cells. Despite these reductions, the levels of apoptosis observed in the same cells are very low and do not account for the reduction in IL-3-dependent proliferation we observe. These results show that Deltap85 inhibits both PKB activity and BAD phosphorylation without significantly affecting levels of apoptosis, suggesting that there are targets other than PKB and BAD that can transmit survival signals in these cells. Our data indicate that the prime target for PI3K action in IL-3 signaling is at the level of regulation of proliferation.  (+info)

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. (3/660)

The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis. The Ca2+-induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-xL resides. In hippocampal neurons, L-glutamate, an inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells.  (+info)

Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro. (4/660)

Survival of immature neurons is regulated by Bcl-xL, as targeted disruption of bcl-x significantly increases cell death in vivo and in vitro. Death of cultured bcl-x-deficient and wild-type telencephalic cells can be prevented by fetal calf serum or chemically-defined medium (ITS), suggesting trophic factors in these media potentiate survival through a pathway independent of Bcl-xL. Addition of trophic factors to basal medium revealed that insulin and insulin-like growth factors (IGFs), but not other trophic factors, reduced apoptosis of wild-type and bcl-x-deficient telencephalic cells. Antibodies raised against IGF-I receptors and wortmannin both attenuated the effects of IGF-I, indicating survival was mediated by IGF-I receptors and phosphatidylinositol 3'-kinase signaling, whereas effects of ITS were only partially reduced by these agents. The survival promoting effects of ITS were reduced in cells lacking both bcl-x and bcl-2, indicating Bcl-2 plays a supportive role to Bcl-xL in maintaining telencephalic cell survival. Furthermore, the ratio of expression of the pro-apoptotic bax gene to the anti-apoptotic bcl-2 gene was reduced in bcl-x-deficient cultures grown in ITS, suggesting that the interaction between these bcl-2 family members may, in part, regulate a Bcl-xL independent survival pathway. Finally, the pro-apoptotic bad gene does not appear to play a role in these interactions as targeted disruption of bad did not alter apoptosis in telencephalic cultures.  (+info)

Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. (5/660)

Signaling pathways between cell surface receptors and the BCL-2 family of proteins regulate cell death. Survival factors induce the phosphorylation and inactivation of BAD, a proapoptotic member. Purification of BAD kinase(s) identified membrane-based cAMP-dependent protein kinase (PKA) as a BAD Ser-112 (S112) site-specific kinase. PKA-specific inhibitors blocked the IL-3-induced phosphorylation on S112 of endogenous BAD as well as mitochondria-based BAD S112 kinase activity. A blocking peptide that disrupts type II PKA holoenzyme association with A-kinase-anchoring proteins (AKAPs) also inhibited BAD phosphorylation and eliminated the BAD S112 kinase activity at mitochondria. Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor.  (+info)

Developmental regulation of Bcl-2 family protein expression in the involuting mammary gland. (6/660)

Epithelial cells within the mammary gland undergo developmental programmes of proliferation and apoptosis during the pregnancy cycle. After weaning, secretory epithelial cells are removed by apoptosis. To determine whether members of the Bcl-2 gene family could be involved in regulating this process, we have examined whether changes in their expression occur during this developmental apoptotic program in vivo. Bax and Bcl-x were evenly expressed throughout development. However, expression of Bak and Bad was increased during late pregnancy and lactation, and the proteins were present during the time of maximal apoptotic involution. Thereafter, their levels declined. In contrast, Bcl-w was expressed in pregnancy and lactation but was downregulated at the onset of apoptosis. Bcl-2 was not detected in lactating or early involuting mammary gland. Thus, the pro-apoptotic proteins Bax, Bak and Bad, as well as the death-suppressors Bcl-x, Bcl-2 and Bcl-w, are synthesised in mouse mammary gland, and dynamic changes in the expression profiles of these proteins occurs during development. To determine if changes in Bak and Bcl-w expression could regulate mammary apoptosis, their effect on cultured mouse mammary epithelial cells was examined in transient transfection assays. Enforced expression of Bak induced rapid mammary apoptosis, which could be suppressed by coexpression of Bcl-w. In extracts of mammary tissue in vivo, Bak heterodimerized with Bcl-x whereas Bax associated with Bcl-w, but Bak/Bcl-w heterodimers were not detected. Thus, Bak and Bcl-w may regulate cell death through independent pathways. These results support a model in which mammary epithelial cells are primed for apoptosis during the transition from pregnancy to lactation by de novo expression of the death effectors Bak and Bad. It is suggested that these proteins are prevented from triggering apoptosis by anti-apoptotic Bcl-2 family proteins until involution, when the levels of Bcl-w decline. Our study provides evidence that regulated changes in the expression of cell death genes may contribute to the developmental control of mammary apoptosis.  (+info)

Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. (7/660)

Protein kinase B lies "downstream" of phosphatidylinositide (PtdIns) 3-kinase and is thought to mediate many of the intracellular actions of insulin and other growth factors. Here we show that FKHR, a human homologue of the DAF16 transcription factor in Caenorhabditis elegans, is rapidly phosphorylated by human protein kinase Balpha (PKBalpha) at Thr-24, Ser-256, and Ser-319 in vitro and at a much faster rate than BAD, which is thought to be a physiological substrate for PKB. The same three sites, which all lie in the canonical PKB consensus sequences (Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr)), became phosphorylated when FKHR was cotransfected with either PKB or PDK1 (an upstream activator of PKB). All three residues became phosphorylated when 293 cells were stimulated with insulin-like growth factor 1 (IGF-1). The IGF-1-induced phosphorylation was abolished by the PtdIns 3-kinase inhibitor wortmannin but not by PD 98059 (an inhibitor of the mitogen-activated protein kinase cascade) or by rapamycin. These results indicate that FKHR is a physiological substrate of PKB and that it may mediate some of the physiological effects of PKB on gene expression. DAF16 is known to be a component of a signaling pathway that has been partially dissected genetically and includes homologues of the insulin/IGF-1 receptor, PtdIns 3-kinase and PKB. The conservation of Thr-24, Ser-256, and Ser-319 and the sequences surrounding them in DAF16 therefore suggests that DAF16 is also a direct substrate for PKB in C. elegans.  (+info)

Cytokine-induced protein kinase B activation and Bad phosphorylation do not correlate with cell survival of hemopoietic cells. (8/660)

Activation of phosphoinositide-3 kinases (PI3Ks), their downstream target protein kinase B (PKB), and phosphorylation of Bad have all been implicated in survival signaling in many systems. However, it is not known whether these events are sufficient or necessary to universally prevent apoptosis. To address this issue, we have used three different factor-dependent hemopoietic cell lines, MC/9, BaF/3, and factor-dependent (FD)-6, which respond to a range of cytokines, to investigate the relationship between PI3K, PKB, and Bad activity with survival. The cytokines IL-3, IL-4, stem cell factor (SCF), GM-CSF, and insulin all induced the rapid and transient activation of PKB in responsive cell lines. In all cases, cytokine-induced PKB activation was sensitive to inhibition by the PI3K inhibitor, LY294002. However, dual phosphorylation of the proapoptotic protein Bad was found not to correlate with PKB activation. In addition, we observed cell-type-specific differences in the ability of the same cytokine to induce Bad phosphorylation. Whereas IL-4 induced low levels of dual phosphorylation of Bad in FD-6, it was unable to in MC/9 or BaF/3. Insulin, which was the most potent inducer of PKB in FD-6, induced barely detectable Bad phosphorylation. In addition, the ability of a particular cytokine to induce PKB activity did not correlate with its ability to promote cell survival and/or proliferation. These data demonstrate that, in hemopoietic cells, activation of PKB does not automatically confer a survival signal or result in phosphorylation of Bad, implying that other survival pathways must be involved.  (+info)

The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. ...
These results indicate that the mechanism by which the US3 protein kinase blocks activation of the BAD protein does not depend on the phosphorylation of the regulatory serines or the interaction of BAD with the 14-3-3 proteins.. In an earlier article this laboratory reported that the US3 protein kinase blocked the apoptosis induced by the HSV-1 d120 mutant at a premitochondrial stage (21). Further studies revealed that the kinase also blocks programmed cell death induced by the proapoptotic protein BAD (22). In the studies reported here, we investigated the effects of the US3 protein kinase on the function and state of the BAD protein. We report several key findings below.. (i) In uninfected cells BAD was processed by at least two proteolytic cleavages that are blocked by caspase inhibitors. The untreated transduced cells expressed elevated caspase 3 activity.. (ii) In cells cotransduced with the US3 protein kinase, the BAD protein was not cleaved and the caspase 3 activity was not ...
TY - CONF. T1 - Artesunate targets the Bcl-2 antagonist of cell death promoter in humans. AU - Karuso, P.. AU - Kwon, H. J.. AU - Gotsbacher, M.. AU - Cho, S.. AU - Kim, N. H.. AU - Liu, F.. PY - 2016. Y1 - 2016. M3 - Abstract. SP - 16. EP - 16. ER - ...
Find and order matched antibody pairs and products like this BAD (phospho S134) & BAD Protein Phosphorylation Antibody... | Jetzt Produkt ABIN1340465 bestellen.
Simple lifestyle choices, such as following a healthy diet and regular exercise, can override bad genes, according to one of Canadas leading genetic researchers.
We cannot help the genes we are born with. Whether good genes or bad genes, we are stuck with the ones our parents passed on to us. I have some bad genes in my blood stream when it comes to heart disease and many of you do, too. But it is possible to overcome some of those bad genes with our diets so that is good news. This information is from two large international studies where researchers looked at heart disease rates in people with gene variations on chromosome 9 which is know to significantly increase ones odds of heart disease. As expected they found that people with the variations had more heart disease. But here is the good news - That was only true if they ate a poor diet! Those who followed healthier diets had no more heart disease than the general population. Those healthier diets involved eating several servings a day of two out of the following categories; fresh fruit, fresh vegetables, and berries. Now how hard is that to do? Pretty simple, right? The research showed that the most ...
We cannot help the genes we are born with. Whether good genes or bad genes, we are stuck with the ones our parents passed on to us. I have some bad genes in my blood stream when it comes to heart disease and many of you do, too. But it is possible to overcome some of those bad genes with our diets so that is good news. This information is from two large international studies where researchers looked at heart disease rates in people with gene variations on chromosome 9 which is know to significantly increase ones odds of heart disease. As expected they found that people with the variations had more heart disease. But here is the good news - That was only true if they ate a poor diet! Those who followed healthier diets had no more heart disease than the general population. Those healthier diets involved eating several servings a day of two out of the following categories; fresh fruit, fresh vegetables, and berries. Now how hard is that to do? Pretty simple, right? The research showed that the most ...
Ive read multiple articles, forum posts and websites. Some say that Nolva and/or Clomid are bad on the lipids, while others say that Nolva and/or
Its been known for years that light drinking benefits the heart, and now, some American and Italian researchers think they know why.
Another Portland big man, Bill Walton, was selected by the Blazers with the No. 1 pick in the 1974 draft, but he was dogged by a broken nose, foot, wrist and leg over his first two seasons before helping the team to the NBA championship in 1977 ...
We have shown that the expression of a number of protective genes and a protective pathway culminating in Bad phosphorylation are increased in mice that overexpress APPSw and have no neuronal loss. Increased levels of IGF-2 mRNA and protein correspond to increased activation of the IGF-1 receptor, activation of Akt and Erk1/2, and phosphorylation of Bad in APPSw mice. The increased expression of TTR and IGF-2 as well as increased phospho-Bad staining in hippocampal neurons was consistent in both preplaque (6 months) and postplaque (12 months) Tg2576 mice. Other conditions, such as the presence of a human tau gene, may be necessary for complete AD pathology. However, taken together, these data imply that the lack of neurodegeneration in APPSw mice is a result of the activation of known cell survival pathways associated with the overexpression of APPSw.. Transthyretin has been shown to bind Aβ and inhibit Aβ aggregation (Schwarzman et al., 1994). In human AD patients the concentration of TTR is ...
The fact is, genetics are a tendency, not a death sentence. Genes for heart disease, breast cancer, mental, emotional disorders, etc., are like the trigger on a gun-theyre only dangerous if you pull them. Inside of just one nucleus in one of your fifty trillion cells is six feet of DNA material. This is similar to cramming thirty miles of wire into a cherry pit. This DNA comes in forty-six different sections called chromosomes, which is subdivided into your genes. These genes encode information for molecules that perform a bewildering number of functions. We barely have a glimpse of the monstrous complexity of genes and how they specifically affect our behaviors and respective biology. To say that a "gene" causes obesity, depression, alcoholism, or chocolate addiction is insane. We truly dont understand 5 percent of whats going on, and that percentage never improves because with each new discovery, we also discover that theres even more mystery.. ...
Scientists have discovered that many cases of low IQ or mental retardation result from random new mutations that arise spontaneously, not from faulty genes inhe
Competence is comfortable - but maybe it shouldnt be. Doing things youre bad at has some serious mental, physical, and emotional benefits.
FACE Bad is an in cell Western method (cell based assay) that includes ELISA reagents and 2 antibodies to monitor levels of both native Bad protein and phospho Bad (S112), which has been activated by kinases (phosphorylation).
FACE Bad is an in cell Western method (cell based assay) that includes ELISA reagents and 2 antibodies to monitor levels of both native Bad protein and phospho Bad (S112), which has been activated by kinases (phosphorylation).
I have good days and i have bad days it really all depends on how much fluid is backing up into my lungs, my day to day life is very much changed in the recent months, im tried all the time a good day i will get through the day without a sleep. my breathing is pretty crappy on a bad day walking around the house is a small mission, taking a shower is a lot of energy on a good day i want have as much fluid on the lungs so i can go out and do stuff maybe only stopping to catch my breath every few 100 meters or not at all, it really does depend each day can be different. Before my transplant on bad days i wouldnt be able to eat and would vomit a lot if a had to much fluid on board which has started to happen again not as much as before transplant but on bad days i havent been able to eat and been vomiting a bit ...
Treasury Secretary Henry M. Paulson and Federal Reserve Chairman Ben S. Bernanke met with congressional leaders to resolve mounting bad loans that have dragged down a beleaguered Wall Street.
Lucy is a perplexing blend of science and fiction. WIRED asked writer/director Luc Besson for all the secrets of his latest film.
This synthetic peptide is phosphorlated on S99 of human BAD and is used as the immunogen for PAB0418. (P1279) - Products - Abnova
Sexuality and Evolution According to a study in the Oct. 19 issue of Science, sex may be a way for you to bring in the good and get rid of the bad. In other words, sex weeds out the bad genes that may have arisen in your DNA -- so-called "baggage" -- and allows good mutations to flourish in your offspring. To test this interesting theory, researchers William R. Rice, PhD, and Adam K. Chippendale looked at two different populations of fruit flies -- one that reproduced with sex and one reproduced without sex. Rice and Chippendale are from the department of ecology, evolution and marine biology at the University of California in Santa Barbara. They found that in flies that had sex, good gene changes were able to spread throughout the population faster than those deprived of the joy of sex. Generally, we think of mutations as being a bad thing, but, in fact, mutations can actually lead to good changes in our bodies. For example, at some point in history, a good gene mutation likely led to some ...
bad_fwdprimers = [bad_fwdprimers_gc, bad_fwdprimers_tm,... bad_fwdprimers_dimers, bad_fwdprimers_hairpin,... bad_fwdprimers_clamp, bad_fwdprimers_repeats]; bad_revprimers = [bad_revprimers_gc, bad_revprimers_tm,... bad_revprimers_dimers, bad_revprimers_hairpin,... bad_revprimers_clamp, bad_revprimers_repeats]; good_fwdpos = find(all(~bad_fwdprimers,2)); good_fwdprimers = fwdprimerlist(good_fwdpos,:); good_fwdprop = fwdprimerprops(good_fwdpos); N_good_fwdprimers = numel(good_fwdprop) good_revpos = find(all(~bad_revprimers,2)); good_revprimers = revprimerlist(good_revpos,:); good_revprop = revprimerprops(good_revpos); N_good_revprimers = numel(good_revprop) figure imagesc([bad_fwdprimers any(bad_fwdprimers,2)]); title(Filtering candidate forward primers); ylabel(Primer location); xlabel(Criteria); ax = gca; ax.XTickLabel = char({%GC,Tm,Dimers,Hairpin,GC clamp,Repeats,All}); ax.XTickLabelRotation = 45; colorbar ...
I have also placed a poll on this which I voted Very bad on, because I dont think its professional in any case. I am just posting to get some thoughts on this. Q) How bad is it for Sky to ignore the
If some gene is harmuful when you are 80 years old (e.g. something that causes cancer), it doesnt mean it is exclusively a bad gene. Many oncogenes, for example, are genetic control elements that have an important role in the life and development of an individual. If you removed them, you would die as a fetus. So can you really call a gene that allows you to become an adult and have children a harmful gene? It may become harmful later on for sure, but it has already done its good deeds. Also it is worth noting that often these harmful genes have simply mutated during the individuals life and become malfunctioning. Evolutionary it is not very disastrous if you die of cancer at the age of 80, if the gene that caused your death was useful the years before that ...
If some gene is harmuful when you are 80 years old (e.g. something that causes cancer), it doesnt mean it is exclusively a bad gene. Many oncogenes, for example, are genetic control elements that have an important role in the life and development of an individual. If you removed them, you would die as a fetus. So can you really call a gene that allows you to become an adult and have children a harmful gene? It may become harmful later on for sure, but it has already done its good deeds. Also it is worth noting that often these harmful genes have simply mutated during the individuals life and become malfunctioning. Evolutionary it is not very disastrous if you die of cancer at the age of 80, if the gene that caused your death was useful the years before that ...
To take or not to take, this is my question. I have one bad gene diagnosed as MTHFR. Doc said the other gene is either compensating or my diet is correcting. I have already lost one pregnancy and two babies (twins). I still load up on vitamines daily. I am starting IVF next week, well I started taking BC pills weeks ago. I am wondering opinions on baby asprin. Doc said it wasnt necessary but others I have read are taking it but perhaps for a different reason, I am not sure. Anyway, will it hurt in any way if I just do take it as a precaution ...
Humorous views on interesting, bizarre and amusing articles, submitted by a community of millions of news junkies, with regular Photoshop contests.
Humorous views on interesting, bizarre and amusing articles, submitted by a community of millions of news junkies, with regular Photoshop contests.
I posted a video earlier that talks about the importance of proper positioning. Take a look at that or maybe even show it to your vet. Heres an article about this which shows at the top right a picture of 2 x-rays, taken 2 months apart of the same dog. One bad position, one good. Take a look at that picture. It reminds me of your x-ray only bad on the opposite side. ...
I am in AP Chemistry and AP U.S Hisotry and I have planned on taking the tests. So far I have made an A+ in APUSH, but I an B in AP Chem. Ive done kinda bad on the tests Ive taken in there and I dont think I will do good on the Ap exam. I think I have a better chance at ... ...
A high-risk patient needed surgery, but Dr Koka couldnt find a surgeon willing to operate on him, for fear of looking bad on publically reported outcomes data.
On bad days, I really do think that modern communications technology really has ushered in something completely new. And maybe it will! But right now, this claim in The Atlantic that it the Internet has created a meaningless post-everything world,...
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You might think youre having bad sex, but even bad sex has its benefits. By changing your expectations and by communicating what it is that you really want, you can have the kind of sex you desire.
You are here: Calculated , Geometry , Bad Calculations , Bad point group OR Resources , Bad Calculations , Geometry , Bad point group OR FAQ Help , List , Geometry , Bad point group ...
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From the Diary as of 1/9/ - 1/31/09 1/17 Bad day - Mom died (my mom) 1/19 - 1/25/09 In my hometown. Preparing things. 1/26 - 1/29/09 It is cold again although we thought winter might go away now after it was relatively mild in my hometown. But the temperatures dropped again severly and it…
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... . A stand that eats your food after you eat it so you don t get the nutrients. Could this be the work of an enemy stand?! No, Jotaro, for the sixth JJBA
REPAIR NOTICE: I originally posted this article earlier this morning but accidentally had some bad data from a dreaded bad sort on Excel. Things should be better now, and the conclusions were affected less than I thought they would be.
Do you attack limiting beliefs though things like positive self-talk ("I know I can do it!") and imaging (imagining ourselves being successful)? I feel those often dont work. The problem is they only address the symptom (convincing yourself not to feel bad) rather than the cause of your limiting belief (why you feel bad in the first place). r. ...
Hi Ladies- Quick relatively new to the group. I have two kids but my husband and I really wanted a third. Turns out he has a low count so they...
Join and connect with BlackPlanets Baby is Bad group. To make it easier for everybody to get to know you please introduce yourselves You can give us a short introduction or tell us a lil more bout
i did a search about premixing protein shakes and leaving them in the fridge and consuming them later....and people say not to do it as the protein
Ive been doing some research about Ragdolls for a few months and Im pretty sure this is the breed that would be suitable for me as I live in a sma
Katherine Heigl has revealed that she was dropped by her own publicist in 2008 following a string of bad press as she consistently exhibited diarrhea of the mouth.
There are some really bad, nasty diseases out there and most of the time, there is nothing good to come of them. For a few diseases though, there are a few bright l...
Hi all, I am new to this group but not new to DS. I was dx with RA 9 years go and after an initial horrible flare was ok for a long while. We were really bad.....
PP-2B inhibition by thioureylenes resulted in a repression of NFAT-dependent gene transcription and thus might influence long-term apoptotic events by limiting the expression of proapoptotic genes (Holtz-Heppelmann et al., 1998). However, NMDA receptor activation, disruption of calcium homeostasis, and PP-2B activation is most probably associated with rapid cell death initiated by proapoptotic Bad proteins (Wang et al., 1999). Thioureylenes inhibited PP-2B-dependent Bad dephosphorylation and the subsequent initiation of the intrinsic pathway of apoptosis (Yang et al., 1995). Thus, caspase-3 activity, cleavage of the cellular caspase-3 substrate PARP, and caspase-3-dependent cell death were inhibited in SK-N-SH cells and organotypic hippocampal slice cultures. These events depended on active PP-2B activation, as demonstrated by coincubation with CsA, a specific PP-2B inhibitor, and included the repression of procaspase-3 processing.. Our results suggest that thioureylenes also attenuate ...
PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. ...
In the popular Pixar Movie "Inside Out", the emotion, Joy, says "[Anger] cares very deeply about things being fair." This becomes apparent when Riley-the protagonist in the film and whose emotions are heavily involved in her decisions-has a difficult time moving to a new city. Anger (pictured above) is first to assume authority and advocates for her to run away! In this impatient and impulsive move, Anger is responsible for Riley stealing her mothers credit card, lying to her parents, and running away from home. Although Riley eventually returns home when Joy and Sadness take control, it is clear that Anger was responsible for a majority of the bad decisions made in the film as he offers little constructive help. There certainly is some truth behind these bad expressions of anger. For instance, research has linked anger with the potential for: (i) aggression and violence; (ii) interpersonal conflicts such as organizational disputes and domestic violence; (iii) impaired judgment, which increases ...
Recently many test has been done with water molecules how they contain memory regarding their surrounding environments how water can show pattern in geometrical shapes of flowers and good or bad expression by sound variations, you can read about it in another article in my Blog subheading "Water H2 0 What is it" Water contain two living energy forces in every hydrogen atoms non biological life force, core of hydrogen Dark Matter as proton invisible bubble clusters and Dark-Energy as millions of invisible group of helixes to form as one electron that later can be separated in fusion to complete other elements, in my article same blog "Neurons" I explained that the main brain that functions in our scull is the lump of water molecules that contain life force, memory, and data to guide biological life forms connecting Universal language in Universe and all sort of stars and planets and atoms connecting into physical cells and monitor to activate their flow of knowledge and developments. Signal ...
The researchers used their AWSEM (Associative memory, Water-mediated Structure and Energy Model) program to analyze how computer models of muscle proteins interact with each other, particularly in various temperatures that determine when a protein is likely to fold or unfold.. The program relies on Wolynes groundbreaking principle of minimal frustration to determine how the energy associated with amino acids, bead-like elements in a monomer chain, determines their interactions with their neighbors as the chain folds into a useful protein.. Proteins usually fold and unfold many times as they carry out their tasks, and each cycle is an opportunity for it to misfold. When that happens, the body generally destroys and discards the useless protein. But when that process fails, misfolded proteins can form the gummy amyloid plaques often found in the brains of Alzheimers patients.. The titin proteins the Rice team chose to study are not implicated in disease but have been well-characterized by ...
Now you have a great excuse for hitting that fire hydrant with your Cadillac Escalade: You- and Tiger Woods-can blame it on bad genes.
Washington D.C. [USA], Jan 15 (ANI): Cannabis consumption can make people bad at driving even when they are sober and the ones who start with the habit early on in their lives, fare even worse on driving parameters.
My dentist prescribes flagyl. I need a root canal and the tooth was infected. Also I am taking a prevpac my dr. prescribed. I am aching all over, dizzy and have a headache. Should I stop taking this? I started friday. I called my dr but she has not returned my call. Please tell me if I should contin (Page 3)
If you're feeling stressed these days, the news media may be partly to blame. At least that's the suggestion of a national survey conducted by
Dallas five-piece The Blurries are riding high from the accolades of last years Paper Cuts. With upcoming appearances at Dada and 35 Denton, bassist...
Rabbit polyclonal antibody raised against synthetic phosphopeptide of BAD. Synthetic phosphopeptide (conjugated with KLH) corresponding to residues surrounding S118 of human BAD. (PAB0415) - Products - Abnova
Strong Bad says "Not even close," very quickly after "Your bestest buddy in the whole wide world," and says "UK" as, "You kay?"} STRONG BAD: {typing} Yeah, Im fine, Gary. Calm down. Of course Ive got the internet. How else could I download this awesome animated gif/gif {Pronounced as /gif/, /jif/} of a cute breakdancing rodent? {A progress bar pops up with a Windows sound that says "11% Complete" with "Less than a fortnight remaining" below} STRONG BAD: {typing} What??!! Eleven percent? I started downloading this thing like two days ago! Oh, thats IT!! Hold on to your fat, sweaty D&D playing headsets, tech support. Cuz Strong Bads about to Do-Sum-Bow-Dis! {The camera rotates around the Lappy to a rear view as Strong Bad picks up the telephone. There is a phone ringing sound and the screen is split by a phone cord with Homestar Runner in the office on the left and Strong Bad on the right. On Homestars cubicle wall there is a Post-It Note that reads "Note to self: Chew more." Homestar wears ...
Tissue from my tumor will be tested (provided insurance agrees to pay for it!) to find out if there are certain markers that will tell us if it is something I inherited. If nothing shows up in the tumor, then there is a different test I can have done that will tell me whether I have this other inherited condition where I get 1 bad gene from each parent. People can be carriers of this gene and not get cancer themselves, but if a child gets 1 from each parent, then that child is likely to get colon cancer. With one of these issues there is a greater chance that I could get other kinds of cancers also, specifically uterine. I guess some women even have their uterus removed to prevent this. So, it would be good to know for myself, and my daughters. ...
A gene is a locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions.[1][2] The physical development and phenotype of organisms can be thought of as a product of genes interacting with each other and with the environment.[3] A concise definition of a gene, taking into account complex patterns of regulation and transcription, genic conservation and non-coding RNA genes, has been proposed by Gerstein et al.[4] "A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products". Colloquially, the term gene is often used to refer to an inheritable trait which is usually accompanied by a phenotype as in ("tall genes" or "bad genes") -- the proper scientific term for this is allele. In cells, genes consist of a long strand of DNA that contains a promoter, which controls the activity of a gene, and coding and non-coding sequence. ...
5. Fellas, Girls really do like assholes: Not all girls like assholes, and I know that the wonderful women who read my blog probably dont, but many women do. I dont even mean to say that "women like assholes" as it being a good thing, it is kind of sad actually. I speak from experience because I couldnt tell you how much women like the fact that I am a insufferable prick. I have actually told women to stay away from me, that I am a asshole, and that I might end up fucking their life up. The usual response is, "Youre funny, heres my number." This one time I was with Danny and I was cursing out the bartender because of something he said to me. Moments later I realized that I had misunderstood him and was about to apologize, but this girl liked how I "handled myself" and wanted to know if I would call her. She just heard me call a grown man belittling names and she finds that attractive?? What the fuck?!! Ladies, if a guy tells you he is bad news it is probably good advice to listen to him ...
And dont be afraid to combine these. Shock them with a scary statistic. Or I typically like to question my audience and then work into a story. Ill sometimes ask my audience who among them has had a bad day in the past month. Typically 80% of the hands in the room will go up. From there Ill share a story about the day I met a man whod had a really bad day Walter Mikak ( who lost both his daughters and his wife in one day in the Port Arthur massacre in Tasmania. After Im done sharing part of Walters remarkable story and the perspective its given me on bad days, Ill ask the same question again - who really has had a bad day in the past month ...
I had not been feeling well after we all had the flu but I kept going because thats what we do. I started feeling really bad on one particular day and I was driving with two of my children and didnt want to take chances on the interstate so I went to an emergency room. A small country emergency room....(Note to reader...I hate Drs so I dont go unless Im pregnant or dying so on this visit I was not pregnant... so I must have thought I was dying..) I was three hours from home and Scott, but I could tell something was not right. I will save you the details of the 6 hour visit but the short of it was my blood pressure was high and the Dr. decided to do a cat scan of my lungs...? Ok I said a little worried but off to the cat scan room I went.. The big machine rolling around me like a dump truck rolling over a pile of dirt. My mind going through the possibilities of all of the "What ifs" in the world. What if Ive had a heart attack? What if.... every bad thing you can imagine went through my ...
Adverse criticism, far from being the easiest, is one of the hardest things in the world to do well. And that for two reasons. When we try to define the badness of a work, we usually end by calling it bad on the strength of characteristics we can find also in good work. . . . The novel before you is bad-a transparent compensatory fantasy projected by a poor, plain woman, erotically starving. Yes, but so is Jane Eyre. . . . An author betrays shocking indifference to all the great political, social, and intellectuals upheavals of his age; like Jane Austen. The solution of the problem is, I suspect, still far away. . . . The other difficulty lies within. . . . Reviews filled with venom have often been condemned socially for their bad manners, or ethically for their spite. I am not prepared to defend them from either charge; but I prefer to stress their inutility. . . . Automatically, without thinking about it ones mind discounts everything [the venomous critic] says, as it does when we are ...
Sure, but theres not a lot of sense involved. You can try 4x10 for a few workouts, then change to 6x8, if you like. I think rep schemes on chins should have some variety. You can do a strict progression (like try to do even sets across), or you can do several sets to failure (going to failure isnt as bad on things like chins as on big lifts like squat and DL), or you can mix it up. Have you tried ladders? Or singles or doubles or triples and see how many sets you can get (you might want to do a set between every set of everything else youre doing). How about a total rep target, like decide that youre going to get 60 (or 80, or 100 or your grandmas age in as many sets as it takes. Or you can use one day a week for a strict progression, and a different day to go for target reps, or something different. Switch in weighted chins once in a while ...
Sure, but theres not a lot of sense involved. You can try 4x10 for a few workouts, then change to 6x8, if you like. I think rep schemes on chins should have some variety. You can do a strict progression (like try to do even sets across), or you can do several sets to failure (going to failure isnt as bad on things like chins as on big lifts like squat and DL), or you can mix it up. Have you tried ladders? Or singles or doubles or triples and see how many sets you can get (you might want to do a set between every set of everything else youre doing). How about a total rep target, like decide that youre going to get 60 (or 80, or 100 or your grandmas age in as many sets as it takes. Or you can use one day a week for a strict progression, and a different day to go for target reps, or something different. Switch in weighted chins once in a while ...
I am on my second round of 50mg Clomid and both times, my vaginsa starts to hurt really bad on the 3rd day of taking the pill. Like, painful, raw, almost like a yeast infection but without the itching or discharge (sorry). Has anyone else experienced similar side effects? I took a Diflucan on the same day that I started to feel these symptoms, so now I feel better, but I am just wondering if this has happened to anyone else. I have googled yeast infections or vaginal pain being a side effect of clomid and I dont really find much that says that it is a known side effect. If I do not get pregnant this round, I am going to ask my RE (reproductive endocrinologist) if we can try Femara next month.
Funny how dreams seem to have recurring themes.. In mine, I am always on my own, there are only one or two persons I deal with directly - though a crowd of nameless people may be involved in some part of the dream -, and I do something crazy and bad on an uncontained compulsion, but there are no immediate consequences, and I get ever more anxious as life continues and I try to pretend nothing happened. The dreams usually end or fizzle out before reaching any conclusion; all there ever is is that ...
Yeah Revere-I cant tell whether there are human cases or not in India….. Its the old dog and pony act. We aint testing so you cant call it BF. We can see pneumonia though. Are there H2H cases? Obviously not in a high path way because if it were, we would be burying people in Europe by about now. Herman-100 human cases… I think he is referring only to the Indon stuff and its not extending in a hard way…yet. I look at the news just before I hit the rack each night because thats when the news is coming in from over there and I get the feeling we are in for it. But, and its a big damn BUT, we havent seen any "official" confirmation of anything but pneumonia. These guys if they are hiding things are gonna be dead and I mean physically if they are sandbagging in these countries. Those people have a more direct input to their electeds and its via a rope and a tree. Every story out of there is right now that no one trusts them. Thats good on one hand and bad on the other. Good because they will ...
I went to visit my pals on Saturday, Kristy, Stacy, Ryan, and Craig. It was, of course, fabulous, and I am seriously aggravated with myself for not taking any pictures. I even remembered my camera this time. How like me. (To forget to take pictures after making sure to remember the camera. Oh geez.) I had to drive a new route there, because obviously Ive never gone there from here before. That was a trick and a half, let me tell you. It took me on all these little roads in the middle of nowhere, roads that werent even county roads. None were labeled. I was a mess, I can assure you. So, I had Chuck find me a better way home. The way he had me go took a little longer, but I was able to stay on actual roads with names. This helped a lot, as it was dark and snowing at this point. Oh, and it saved my life. Apparently, it was really bad on 74 just before I got to it. When I made it onto 74, traffic was crawling (people averaging 35 mph.) I saw two cars that had flipped over, and I lost count of all ...
But I was making a big mistake. I had kept hearing that its simple, what you take in needs to match what you put out, plus some. So if you eat big meals, but dont exercise, that food has got to go somewhere, like on your frame, probably as fat. Im not a big fan of carrying around extra fat. I mean, why? Right? What do you need it for, other than to rationalize why you dont have to work to get rid of it? Fat isnt attractive, its bad on your body, your joints, your self-esteem, and the nations infrastructure to be honest. Airplanes dont need to carry our lard around, wasting fuel, adding to carbon emissions. Cars dont need to be lugging around our bulk, wearing them out slowly along with our roads and bridges. We are costing our nation a lot of money year in and year out with all the unnecessary fat we are carrying about. So, why not lose it? You may even live longer ...
Futures are fighting with mixed results to move higher this morning, as the Dow comes off its worst week of the year. The index fell 30-points on Friday. Not that bad on its own, but the move lower followed a … Continue reading →
Oxygen to debut fourth Bad Girls Club edition on Dec. 1, reveals cast. Oxygen has revealed the identities of the seven feisty females who will be appearing on Bad Girls Clubs fourth season, which will premiere Tuesday, December 1 at 10PM ET/PT.
Activists like Brian Bates, who trails prostitute-seeking men, are pointing the cameras on bad behavior in public and posting the exploits online for all the world to shame.
First im not trying to sell anything. Im hoping to use this thread to post trades and get critiqued on bad trades. Feel free to call me out and say WTF...
Central bank issues plan to develop card payment, Financial stocks lift market, VAMC increases rates on bad debts it purchased, Sacombank launches Visa Platinum Cashback credit card
I am sure I have mentioned before that Chhori is still night feeding on a good night, she wakes up 1-2 times for a feed while on bad ones it is multiple times. This routine didnt bother me when I was home looking after her but since I started work, it started affecting my day.…
Night feed she would sometimes wake to have one feed after a 4 to 5 hourly stretch. On bad days, she wakes twice or more. But that hardly happens . Thankful for that ! But during the one month when she still have her jaundice, we do wake her up for milk so that her body is well hydrated and she can flushed it out through the pee ...
The Seventies! It wasnt all bad. In fact, it wasnt that bad at all - especially if you were a kid. Sure, we didnt have the internet, PlayStations or Justin Bieber. But we did have Play School, Dymo...
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It has been a long and stressful past few days, but I am finally back in my own house with my own noises and my own foods. Actually, the past few days werent really that bad at all. The worst day was yesterday. Yesterday morning, around 4 A.M., I woke up and decided that I was going to be sick. So my feet carried me to the toilet, and up came whatever small dinner I had had earlier. Pleasant. My nurse came and brought me some anti-nausea medication called Ativan, which is one of the really heavy duty ones. Basically, it knocked me out for the rest of the day. I threw up two more times throughout the morning, but they put more medication in me, as well as more chemo, and I literally slept all day. So like I said, now Im home. I dont feel great; I have certainly had better days, but Im glad to be out of the hospital. Im currently working through a little bit of nausea and a fair amount of tiredness, but Im sure Ill be back to happy after a good dinner and a good nights sleep. It is ...
Anyone else have this problem?? I have to pee pretty bad at least once an hour...Even worse,I always feel thirsty ,so when I drink water,have have to pee like...
I got some 2XU Knee-High compression socks because my friend (who suffered from severe calf cramping regularly) recommended the things to me because I tend to cramp bad at the end of long distances. I must admit - I was very skeptical at first, but my first 60 miler after taking 2 months off - I had no cramping. Now - after the same exact ride - I took off the sock - and the moment the compression fell off of my calves - a severe cramp came on. I have been continuing the use of it and its very simple for me - I cramp on the rides I do not have them on - and I dont cramp when I do have them on ...
When I was in primary school, a teacher of mine tried to put me forward to run a hurdles race at a county schools championship. I wouldnt let him. Although I really enjoyed the hurdles and wasnt bad at it (I was tall for my age and the hurdles were quite low!), the idea of…
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bodhi, update to Kernel 4.13.2 worked well. Only issue, fw_printenv gives me a bad crc fw_printenv Warning: Bad CRC, using default environment bootargs= bootcmd= bootdelay=2 baudrate=115200 arch=sandbox cpu=sandbox board=sandbox board_name=sandbox stdin=serial,cros-ec-keyb,usbkbd stdout=serial,vidc
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Do You Have Good Days And Bad Days? Join 1,544 friendly people sharing 47 true stories in the I Have Good Days and Bad Days group. Find forums, advice and chat with groups who share this life experience.
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I review the new pre workout from Transparent Labs. This pre workout tastes bad and looks bad, but performs strangely good. Get the full scoop in this review.
Bad Brains were a brilliant 80s band from Washington, DC, also the home of contemporaries Minor Threat. They fused together high-speed punk (the group i...
Arranging plans in Bad Vilbel? Whether youre a local, new to town, or just passing through, youll be sure to find something on Eventbrite that piques your interest.
Talk about confusing. In the world of natural, real food lovers, pork is a contentious subject! So, where was the truth? Is pork bad for you? Is it really unhealthy?
Talk about confusing. In the world of natural, real food lovers, pork is a contentious subject! So, where was the truth? Is pork bad for you? Is it really unhealthy?
"Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death". Adv. Exp. Med. Biol. 406: 99-112. ... Like most protein kinases, c-Raf has multiple substrates. BAD (Bcl2-atagonist of cell death) is directly phosphorylated by c- ... Wang HG, Takayama S, Rapp UR, Reed JC (July 1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1 ... Wang HG, Rapp UR, Reed JC (November 1996). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell. 87 (4): 629-38. doi: ...
"Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins". Cell. 79 (2): 341-51. doi:10.1016/ ... it interacts with the E1B 19 kDa protein which is responsible for the protection of virally induced cell death, as well as E1B ... BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 is a protein that in humans is encoded by the BNIP2 gene. This gene is ... Low BC, Lim YP, Lim J, Wong ES, Guy GR (November 1999). "Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by ...
Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with ... "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes Dev. 19 (11): ... The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript ... Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene. ...
The Bcl-2 Database. *DeathBase: a database of proteins involved in cell death, curated by experts ... BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl-2. Bcl-xL. ... Examples of viral Bcl-2 proteins include the Epstein-Barr virus BHRF1 protein and the adenovirus E1B 19K protein.[95] Some ... The adenovirus E1B-55K protein and the hepatitis B virus HBx protein are examples of viral proteins that can perform such a ...
Members of the Bcl-2 family of pro-apoptotic proteins can induce the opening of the VDAC (12). This will cause the same release ... Mutations of the cell pathway can either promote cell death or disallow cell death creating a huge amount of disease in the ... Role of Bcl-2 Family Proteins in Apoptosis: Apoptosomes or Mitochondria?" Genes to Cells 3.11 (1998): 697-707. Pan, G.; ... Scientists have found that binding depressors to Bcl-2 anti-apoptotic proteins inhibits them and leaves direct activators free ...
"Loss of Prkar1a leads to Bcl-2 family protein induction and cachexia in mice". Cell Death and Differentiation. 21 (11): 1815-24 ... CNC patients have also been discovered with an unusually shortened PRKAR1α protein, detected in tumours and leukocytes, ... "Mutations of the gene encoding the protein kinase a type I-alpha regulatory subunit in patients with the Carney complex". ... which is the gene encoding the regulatory R1α subunit of protein kinase A. Germline heterozygous PRKAR1α inactivation mutations ...
... a Novel Death-Promoting Transcriptional Repressor That Interacts with Bcl-2-Related Proteins". Mol Cell Biol. 19 (6): 4390-404 ... Bcl-2-associated transcription factor 1 is a Bcl-2 family protein in humans that is encoded by the BCLAF1 gene. This gene ... Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein ... "Protein Kinase C δ Induces Transcription of the TP53 Tumor Suppressor Gene by Controlling Death-Promoting Factor Btf in the ...
... a novel death-promoting transcriptional repressor that interacts with Bcl-2-related proteins". Molecular and Cellular Biology. ... "Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo". Proceedings of ... "Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo". Proceedings of ... "Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R ...
... a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death". Oncogene. 18 (46): 6183-90. doi:10.1038/sj.onc. ... "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein". Biochemical and ... BAG3 balances protein synthesis and protein degradation under mechanical stress. PLCG1 has been shown to interact with: FGFR1, ... Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, Kondo S, Bono H, Okazaki Y, Hayashizaki Y (Oct 2001). "Protein-protein ...
Activator of apoptosis Hrk regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L). The HRK ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO ... "Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32". Cell Death Differ ... HRK interacts with BCL2 and BCLXL via the BH3 domain, but not with the death-promoting BCL2-related proteins BAX, BAK, or BCLXS ...
Two models suggest SOD1 inhibits apoptosis by interacting with BCL-2 proteins or the mitochondria itself. The SOD1 enzyme is an ... Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required ... "Modified expression of Bcl-2 and SOD1 proteins in lymphocytes from sporadic ALS patients". Neuroscience Letters. 399 (3): 186- ... "Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria". ...
"Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c". Molecular and Cellular Biology. ... and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein ... two death-signaling proteins released into the cytoplasm by the mitochondria. Smac/DIABLO, a mitochondrial protein and negative ... The protein is also called human IAP-like Protein (hILP), because it is not as well conserved as the human IAPS: hIAP-1 and ...
... a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death". Cell Death and ... The two halves of the protein pack against each other in a clam-shell fashion, sealing via interactions at the ends of the ... There are several MFS proteins in humans, where they are known as solute carriers (SLCs) and atypicla SLCs. There are today 52 ... These protein energetically drive transport utilizing the electrochemical gradient of the target substrate (uniporter), or act ...
1997). „Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death". Adv. Exp. Med. Biol. 406: ... Protein kinaza C (EC Protein kinaza C, Protein kinaza Cζ, PKC alfa, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley- ... Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ...
Oxidative stress can directly cause neuron cell death or it can trigger a cascade of events that leads to protein misfolding, ... Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. Lithium has been shown to ... Potentially neuroprotective trophic factors include CNTF, IGF-1, VEGF, and BDNF Anti protein aggregation agents: Protein ... "Anti-protein aggregation is a potential target for preventing delayed neuronal death after transient ischemia". Med. Hypotheses ...
... a novel Bcl-2-binding protein with anti-cell death activity". Cell. 80 (2): 279-84. doi:10.1016/0092-8674(95)90410-7. PMID ... The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The ... Wang HG, Takayama S, Rapp UR, Reed JC (July 1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1 ... Wang HG, Takayama S, Rapp UR, Reed JC (1996). "Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1". Proc ...
Yulug IG, See CG, Fisher EM, Ylug IG (1995). "The DAD1 protein, whose defect causes apoptotic cell death, maps to human ... one of the bcl-2 protein family". J. Biochem. 128 (3): 399-405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. ... DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in ... one of the bcl-2 protein family". J. Biochem. 128 (3): 399-405. doi:10.1093/oxfordjournals.jbchem.a022767. PMID 10965038. ...
"Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein". Biochem. Biophys ... This protein is a member of the Hsp70 family. In conjunction with other heat shock proteins, this protein stabilizes existing ... In order to properly fold non-native proteins, this protein interacts with the hydrophobic peptide segments of proteins in an ... As a Hsp70 protein, it has a C-terminal protein substrate-binding domain and an N-terminal ATP-binding domain. The substrate- ...
Apoptosis Apoptosome Bcl-2 Bcl-2-associated X protein (BAX) BH3 interacting domain death agonist (BID) Caspases Cytochrome c ... is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by ... The PUMA protein is part of the BH3-only subgroup of Bcl-2 family proteins. This group of proteins only share sequence ... Biochemical studies have shown that PUMA interacts with antiapoptotic Bcl-2 family members such as Bcl-xL, Bcl-2, Mcl-1, Bcl-w ...
2001). "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein". Biochem ... This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death ... The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that ... Frisch SM (2000). "Evidence for a function of death-receptor-related, death-domain-containing proteins in anoikis". Curr. Biol ...
These proteins are normally involved in host apoptosis or autophagic death and possess a Bcl-2 homology domain 3. ApoL1 has ... The protein components of TLF-1 are haptoglobin related protein (HPR), apolipoprotein L-1 (apoL-1) and apolipoprotein A-1 (apoA ... The gene encodes a protein of 383 residues, including a typical signal peptide of 12 amino acids. The plasma protein is a ... These three proteins are colocalized within spherical particles containing phospholipids and cholesterol. The protein ...
Bcl-2 is an important family of intracellular proteins that helps regulate apoptosis, or cell suicide. Bcl-2, paired with other ... One of the main focuses of their cancer cell research is on cell proliferation and cell death. In particular, the oncoprotein ... The caspases, a type of protease, remain inactive until signaled through a cascade to degrade the proteins that make up a cell ... Myc and the Bcl-2 protein family are of interest to her current research lab. ...
1995). "Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity". Cell. 80 (2): ... The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that ... functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase ... steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a ...
1995). "Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity". Cell. 80 (2): ... This term, derived from the Greek for "against death" ('athánatos), was incorporated into name of the gene Bcl-2-associated ...
... blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. ... Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to ... The apparent volume of distribution for venetoclax is approximately 256-321 L. It is highly bound to human plasma protein. ...
Cell Death Differ". 5, s. 1062-1075, 1998. *↑ Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. „ ... Towards a proteome-scale map of the human protein-protein interaction network. „Nature". 437 (7062), s. 1173-8, 2005. DOI: ... Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent ... a b Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM, Ariga H. TOK-1, a novel p21Cip1-binding protein that ...
The BCL-2 protein family: opposing activities that mediate cell death.. Youle RJ1, Strasser A. ... Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying ... BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade ... B-cell lymphoma 2 (Bcl-2) protein family - overview and references - Guide to Pharmacology ...
The Bcl-2 family of proteins is a major cell death regulator and is implicated in determining the survival or death of neurons ... Tsujimoto, Y. and Shimizu, S. VDAC regulation by the Bcl-2 family of proteins. Cell Death Diff. 7: 1174-1181,2000CrossRefGoogle ... Tsujimoto Y. (2002) Regulation of Cell Death by the Bcl-2 Family of Proteins. In: Nagatsu T., Nabeshima T., McCarty R., ... Tsujimoto, Y. and Shimizu, S.: Bcl-2 family: Life-or-death switch, FEBS lett. 466: 6-10, 2000PubMedCrossRefGoogle Scholar ...
... pathway of cell death controlled by the BCL-2 family of proteins. BCL-2 inhibits cell death induced by erlotinib, but BCL-2- ... cell death pathway controlled by the BCL-2 family of proteins. BCL-2, which protects against mitochondrial cell death, inhibits ... BCL-2, along with related cellular antiapoptotic proteins BCL-XL, BCL-w, BFL-1, and MCL-1 interfere with the progression of ... BCL-2 could prevent this death, at the expense of rendering the cell newly dependent on BCL-2 function. Protection by BCL-2 ...
The anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-xL, Bcl-w, Mcl-1, A1, Boo/Diva/Bcl-2-L10, Bcl-B and C. elegans CED-9 ... elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93, 519 -529. ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-XL. EMBO J. ... Adams, J. M. and Cory, S. ( 2001). Life-or-death decisions by the Bcl-2 protein family. Trends Biochem. Sci. 26, 61 -66. ...
Editors ethnic bcl 2 protein family essential regulators of cell death, Initials. A war for according Dutch PDFbooks. top- ... Bcl 2 Protein Family Essential Regulators Of Cell Death. by Hester 3 ... Bcl 2 Protein Family Essential Regulators Of Cell Death. td,div,span { font-family:arial; font-size:14px; color:#5B3535; } a,a: ... There Know no bcl 2 protein family essential regulators of frontiers on this Theory still. University of Kent 1984) is ...
Caspase-Independent Death. While most pro-apoptotic proteins probably directly antagonize pro-survival proteins via their BH3 " ... Bok, for example, interacts with Mcl-1 and the Epstein-Barr viral protein BHRF1 but not with Bcl-2, Bcl-xL, or Bcl-w (24). ... revealed that Bax is responsible for much of the neuronal death in bcl-x−/− mice and the lymphoid in bcl-2−/− mice. ... Bcl-xL, Bcl-2, and Bax do form channels in lipid bilayers in vitro, and those created by Bax and Bcl-2 have distinct ...
It covers programmed cell death, cell death induced by toxic agents, differentiation and their relation to cell proliferation. ... Cell death and Differentiation provides an accessible source of up-to-date information for scientists and clinicians. ... non-lethal functions of BCL-2 family proteins, and alternative, caspase-independent developmental cell death pathways. ... Welcome to Cell Death & Differentiation Devoted to the cell biology, molecular biology and biochemistry of cell death and ...
Apoptosis Apoptosome Bcl-2 BH3 interacting domain death agonist (BID) Caspases Cytochrome c Noxa Mitochondrion p53 upregulated ... also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ... Bcl-2-associated X protein has been shown to interact with: Bcl-2, BCL2L1, BCL2A1 SH3GLB1, SLC25A4, VDAC1, TCTP, YWHAQ, Bid, ...
Bcl-2 family member Bcl-G is not a proapoptotic protein. [Cell Death Dis. 2012] Bcl-2 family member Bcl-G is not a proapoptotic ... LSBio BCL2L14 / BCL-G Proteins [LifeSpan BioSciences, Inc.] LSBio BCL2L14 / BCL-G Proteins. LifeSpan BioSciences, Inc. ... apoptosis facilitator Bcl-2-like protein 14 [Mus musculus] apoptosis facilitator Bcl-2-like protein 14 [Mus musculus]. gi, ... Detection of Bcl-2 family member Bcl-G in mouse tissues using new monoclonal antibodies. [Cell Death Dis. 2012] Detection of ...
Bcl-2-family proteins are central regulators of cell life and death. At least three major classes of Bcl-2-family proteins have ... of the Bcl-2 family include Bax, Bak, and Bok. The founding member of the MDP group of Bcl-2-family proteins was discovered by ... Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities.. Reed JC1. ... Stanley Korsmeyer and co-workers, initiating an exciting area of cell death research. The status of current knowledge about the ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death- ... Protein Feature View of PDB entries mapped to a UniProtKB sequence * Number of PDB entries for Q13323: no matching PDB entries ... This protein in other organisms (by gene name): Q13323 - Homo sapiens 0 * O70337 - Mus musculus no matching PDB entries ...
A: Cell death triggered by ABT-737 is caspase dependent. Noxa-expressing wild-type MEFs were treated with ABT-737 (1 μM) and ... Despite its high affinity for Bcl-2, Bcl-x(L), and Bcl-w, many cell types proved refractory to ABT-737. We show that this ... ABT-737 potently sensitizes cells overexpressing Bcl-2 to genotoxic agents. A: Bcl-2 or Bcl-xL overexpression renders FDC-P1 ... B, C: FDC-P1 cells overexpressing Bcl-2 (B) or Bcl-xL (C) were treated with ABT-737 (0-10 μM), and Etoposide (25μM) or Cytosine ...
Poly-ubiquitinated protein aggregate formation is the most striking hallmark of various neurodegenerative diseases such as ... Defining the role of the Bcl-2 family proteins in Huntingtons disease. Cell Death Dis 4:e772. doi: 10.1038/cddis.2013.300 ... Bcl-2 Decreases the Affinity of SQSTM1/p62 to Poly-Ubiquitin Chains and Suppresses the Aggregation of Misfolded Protein in ... Tsai HF, Tsai HJ, Hsieh M (2004) Full-length expanded ataxin-3 enhances mitochondrial-mediated cell death and decreases Bcl-2 ...
SidF Inhibits Cell Death Induced by Bcl-rambo.. A common feature for antiapoptotic proteins that target pro-death proteins is ... or for proteins such as BNIP3 and Bcl-rambo. Given that BNIP1, a pro-death BH3-only protein of the BNIP3 family is involved in ... SidF Interacts with BNIP3 and Bcl-rambo, Two Pro-Death Members of the Bcl2 Protein Family.. SidF is not homologous to any known ... 4 F); third, SidF did not detectably interact with several other pro-death proteins structurally similar to BNIP3 and Bcl-rambo ...
Binding to the apoptosis repressors Bcl-X(L), BHRF1 or Bcl-2 suppresses this death-promoting activity. ... "Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.". Hegde R., Srinivasula S. ... "Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.". Hegde R., Srinivasula S. ... "Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.". Hegde R., Srinivasula S. ...
This project investigates a group of genes that regulate cell death and that can contribute to tumour development and sustained ... This project investigates a group of genes that regulate cell death and that can contribute to tumour development and sustained ... Investigating the requirement of pro-survival Bcl-2 family proteins in leukaemia Lead researcher. Dr Stephan Glaser ...
Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death- ... Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death- ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. Q13323. A0A024R4X6. Homo sapiens (Human). 160. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ...
The Bcl-2-associated death promoter (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in ... "The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2". Cell Death ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO ... bcl-Associated Death Protein at the US National Library of Medicine Medical Subject Headings (MeSH) Human BAD genome location ...
In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins ... the Bcl-2-related proteins can be separated into anti-apoptotic (Bcl-2, Bcl-xL, Mcl-1, Bcl-w, and Bfl-1/A1) and pro-apoptotic ... Bcl-xL, and Bcl-w. We further tested interactions between Bok and several pro-apoptotic Bcl-2 proteins (Fig. 2A). Of interest, ... Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic proteins. Coupled with findings showing that Bok-induced apoptosis could only be ...
Furthermore, inhibition of Bcl-2 anti-apoptotic family proteins with small molecules antagonists decreases protective effects ... FAM3B/PANDER inhibits cell death and increases prostate tumor growth by modulating the expression of Bcl-2 and Bcl-XL cell ... FAM3B/PANDER inhibits cell death and increases prostate tumor growth by modulating the expression of Bcl-2 and Bcl-XL cell ... Ogura T, Tanaka Y, Tamaki H, Harada M. Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate ...
R-MMU-111453. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members. R-MMU-193648. NRAGE signals death ... R-MMU-111453. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members. R-MMU-193648. NRAGE signals death ... View protein in InterPro. IPR014771. Apoptosis_Bim_N. IPR017288. Bcl-2-like_11. IPR015040. Bcl-x_interacting_BH3_dom. IPR036834 ... View protein in InterPro. IPR014771. Apoptosis_Bim_N. IPR017288. Bcl-2-like_11. IPR015040. Bcl-x_interacting_BH3_dom. IPR036834 ...
Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the ... Potent inhibitor of cell death. Inhibits activation of caspases. ... Bcl-2-like protein 1. Bcl-2-like protein 1 (Bcl-xbeta) ( ... Protein-protein interaction databases. BioGridi. 246998, 5 interactors. ComplexPortali. CPX-2022 BAD:BCL-XL complex [P53563-1] ... protein heterodimerization activity Source: RGDInferred from physical interactioni*. "Bok is a pro-apoptotic Bcl-2 protein with ...
... and anti-apoptotic members of the Bcl-2 protein family. The functions of these Bcl-2 family members are clear in terms of order ... Mitochondrial protein import: a matter of death?. Paschen SA1, Weber A, Häcker G. ... while the anti-apoptotic Bcl-2-like proteins prevent this activation. However, the molecular details are still insufficiently ... We have recently presented evidence that targeting to mitochondria of at least one BH3-only protein is essential for its pro- ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ...
A membrane protein called Bcl-2 inhibits apoptosis. Marie Hardwick of Johns. Hopkins Medical Institutions in Baltimore decided ... A PROTEIN that prevents cell death can switch roles and become an. executioner, says a report in last weeks Science (vol 278, ... Hardwick thought caspase would merely remove Bcl-2s inhibitory effect. But. surprisingly, Bcl-2s cleaved products themselves ... The protein fragments also stimulated more caspase activity, creating a. deadly feedback loop. Hardwick hopes to find out how ...
  • Taken together, by activating pro-survival mechanisms FAM3B overexpression contributes to increased resistance to cell death and tumor growth in nude mice, highlighting a putative role for this cytokine in prostate cancer progression. (
  • Heat shock protein 70 is an antiapoptotic chaperone protein highly expressed in human breast tumors and tumor cell lines. (
  • Bcl-2 and its homologue Bcl-XL are expressed in a variety of tumors and their expression modulates the sensitivity of tumor cells to a wide spectrum of chemotherapeutic agents and γ-irradiation. (
  • 12 Importantly, we reported that HGF linking to c- met , a tyrosine kinase receptor, can act as a protective factor against endothelial cell death induced by serum-free treatment, tumor necrosis factor-α treatment, and high-glucose conditions. (
  • Similar to Bcl-2, Bcl-xL has been implicated in the survival of cancer cells by inhibiting the function of p53, a tumor suppressor. (
  • Furthermore, this protein enhances antigen-specific tumor immunity by facilitating more efficient antigen presentation to cytotoxic T cells. (
  • This protein was found to be associated with the death domain of tumor necrosis factor receptor type 1 (TNF-R1) and death receptor-3 (DR3), and thereby negatively regulates downstream cell death signaling. (
  • Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. (
  • Its activity is strongly regulated within the cell by tumor-suppressant proteins that form the TSC complex. (
  • Tuberous sclerosis is an autosomal recessive disease in which the genes required to express the tumor-suppressant proteins that form the TSC complex is mutated or missing, so the TSC complex is unable to function properly. (
  • These mimetics are also designed to target tumor cells directly through interacting with inflammatory proteins, such as IL-1β, which are commonly produced by solid tumor lesions. (
  • Notably, preclinical studies indicate that the use of SMAC mimetics in conjunction with chemotherapy, death receptor ligands and agonists, as well as small molecule targeted drugs enhance the sensitivity of tumor cells to these treatments. (
  • HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a complex between alpha-lactalbumin and oleic acid that induces cell death in tumor cells, but not in healthy cells. (
  • This protein may function simultaneously with BNIP3 and may play a role in tumor suppression. (
  • Survival occurs when recruited cytoplasmic adaptor proteins facilitate signal transduction through tumor necrosis factor receptor members such as TRAF6, which results in the release of nuclear factor κB (NF-κB) transcription activator. (
  • Translationally controlled tumor protein (TCTP) is a highly conserved protein found in eukaryotes, across animal and plant kingdoms and even in yeast. (
  • Translationally Controlled Tumor Protein (TCTP/tpt1) is a regulator of the cancer stem cell compartment, the tumor reversion program, tumor progression and certain forms of inflammatory diseases. (
  • Human translationally controlled tumor protein (hTCTP) is a growth-related, calcium-binding protein. (
  • Translationally controlled tumor protein was first discovered in 1989 as a cDNA sequence obtained from a human mammary carcinoma cDNA library with proves derived from the translationally controlled, growth-related mouse tumor protein TCTP. (
  • TCTP was originally described as a growth related protein of tumor cells. (
  • Research in 1997 shown that TCTP is not a tumor- or tissue-specific protein, but is expressed ubiquitously from plants to mammals TCTP is a 20-25 kDa protein abundantly and ubiquitously expressed in the cell. (
  • Expression levels of TCTP were down-regulated at the mRNA and protein levels during tumor suppression and by the activation of p53 and Siah-1 very well known anti-tumor genes. (
  • Translationally-controlled tumor protein has a role in tumor reversion and development. (
  • Translationally Controlled Tumor Protein (TCTP) is involved in a wide range of molecular interactions with biological and nonbiological partners of various chemical compositions such as proteins, peptides, nucleic acids, carbohydrates, or small molecules. (
  • An analysis of 196 tumor specimens from patients with renal cell carcinoma found that high tumor expression of PD-L1 was associated with increased tumor aggressiveness and a 4.5-fold increased risk of death. (
  • In the cell nucleus, the protein MUC1 regulates the activity of transcription factor complexes that have a documented role in tumor-induced changes of host immunity. (
  • Various dependence receptors are involved in a range of biological events: developmental cell death (naturally occurring cell death), trophic factor withdrawal-induced cell death, the spontaneous regression characteristic of type IV-S neuroblastoma, neurodegenerative cell death, inhibition of new tumor cells (tumorigenesis) and metastasis, and therapeutic antibody-mediated tumor cell death, as well as programmed cell death in other instances. (
  • Since these receptors may support either cell death or cell survival, they initiate a new type of tumor suppressor, a conditional tumor suppressor. (
  • Tsujimoto, Y Prevention of neuronal cell death by Bcl-2. (
  • Cell Death Diff. (
  • BCL-2 inhibits cell death induced by erlotinib, but BCL-2-protected cells are thus rendered BCL-2-dependent and sensitive to the BCL-2 antagonist ABT-737. (
  • These proteins have evolved to recognise distinct forms of cell stress. (
  • Apoptotic cell death is characterised by a series of morphological and biochemical changes such as plasma membrane blebbing, chromatin condensation, internucleosamal DNA cleavage and exposure of phospatidyl serine on the extracellular side of the plasma membrane. (
  • Penetrating genetic analysis of the nematode Caenorhabditis elegans revealed two loci, ced-3 and ced-4 , essential for programmed cell death during worm development, and a third, ced-9 , that could prevent their action ( 5 ). (
  • Pathways to cell death in C. elegans and mammals. (
  • Access the latest web focus which highlights some of the latest research from China covered by the three journals in the Cell Death portfolio. (
  • Cell Death Dis. (
  • Cell Death Differ. (
  • Accelerates programmed cell death. (
  • Despite its high affinity for Bcl-2, Bcl-x(L), and Bcl-w, many cell types proved refractory to ABT-737. (
  • This project investigates a group of genes that regulate cell death and that can contribute to tumour development and sustained tumour growth after therapy. (
  • Permissive macrophages harboring a replicating sidF mutant are more apoptotic and more sensitive to staurosporine-induced cell death. (
  • Programmed cell death plays an important role in the defense against pathogens, and manipulation of host cell apoptotic processes could determine the outcome of the interplay between the host cell and a pathogen ( 1 ). (
  • Many pathogens have thus evolved various sophisticated strategies to manipulate the execution of programmed cell death pathways for successful colonization of the host. (
  • Similarly, some bacterial pathogens such as Chlamydia trachomatis and Bartonella henselae suppress cell death in infected cells ( 2 , 3 ). (
  • In mammalian cells, infection by L. pneumophila leads to the activation of two independent cell death pathways. (
  • Instead, macrophages harboring actively replicating L. pneumophila exhibit strong resistance to exogenous cell death stimuli ( 16 ). (
  • In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins are critical in the determination of cell fate. (
  • Cell killing induced by Bok was also suppressed following coexpression with Mcl-1 and BHRF1 but not with Bcl-2, further indicating that Bok heterodimerized only with selective anti-apoptotic Bcl-2 proteins. (
  • In reproductive tissues that are characterized by cyclic functional changes, massive cell death occurs under the control of hormonal signals. (
  • The protooncogene Bcl-2 was isolated at the breakpoint of the t(14, 18) chromosomal translocation associated with follicular B-cell lymphoma ( 9 ). (
  • Through heterodimerization, the balance between pro- and anti-apoptotic Bcl-2 proteins presumably determines the cell fate ( 3 , 13 ). (
  • Culture growth and viability of DU145 cell line were evaluated after treatment with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial host. (
  • DU145 cell viability and survival increased after exogenous treatment with recombinant FAM3B protein or FAM3B-secreted protein. (
  • Potent inhibitor of cell death. (
  • Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. (
  • We validated bcl-2/SLIRP interaction by immunoprecipitation and immunofluorescence experiments in cancer cell lines from different histotypes. (
  • The most common resolution of viral infection is by an effective cell-mediated immune response, requiring the virus to escape to new hosts before immunological resolution or before death of the host itself. (
  • These findings suggest that Bax may contribute to neuronal cell death in AD. (
  • Deletion of the BH1, BH2, or BH4 domains of Bcl-2 abolishes its ability to suppress cell death in mammalian cells and prevents homodimerization of these mutant proteins, though these mutants can still bind to the wild-type Bcl-2 protein. (
  • These mutants also fail to bind to BAG-1 and Raf-1, two proteins that we have shown can associate with protein complexes containing Bcl-2 and which cooperate with Bcl-2 to suppress cell death. (
  • Thus, Bcl-2 may suppress cell death at least in part by binding to Bax via the BH3 domain and thereby preventing formation of Bax/Bax homodimers. (
  • J.C. Reed, Bcl-2 and the regulation of programmed cell death, J. Cell Biol . (
  • J. Reed, C. Stein, S. Haldar, C. Subasinghe, C. Croce, S. Yum and J. Cohen, Antisense-mediated inhibition of Bcl-2 proto-oncogene expression and leukemic cell growth: Comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides, Cancer Res . (
  • One distant member, BAD, heterodimerizes with BCL-X(L) or BCL-2, neutralizing their protective effect and promoting cell death. (
  • Only the nonphosphorylated BAD heterodimerized with BCL-X(L) at membrane sites to promote cell death. (
  • Since its discovery in the 1970s, the mitochondrial permeability transition (MPT) has been proposed to be a strategic regulator of cell death. (
  • This review focuses on the most recent advances in understanding mPTP regulation in cancer and highlights the ability of the mPTP to impede the mechanisms of cell death. (
  • The interest in this unusual mitochondrial state increased exponentially in the 1990s after the MPT was shown to be a strategic regulator of cell death ( 2 ). (
  • It would be insufficient and inaccurate to assume that the MPT only results in necrotic cell death. (
  • A role for the MPT in apoptotic cell death has been supported by several studies. (
  • The MPT inhibitor bongkrekic acid ( 14 ) inhibits cell death, while the MPT inducer atractyloside ( 9 ) renders the cell more susceptible to cell death. (
  • Additionally, the proapoptotic protein B-cell lymphoma (BCL)-associated X (Bax) can induce loss of the ΔΨmt in a CsA-sensitive manner ( 15 , 16 ). (
  • The invention provides a method of treating a disease or pathological condition resulting in apoptotic cell death. (
  • Methods to identify compounds that alter apoptotic cell death and to enhance monoclonal antibody production are also provided by the invention disclosed herein. (
  • Resistance to anti-microtubule drug-induced cell death is determined by regulation of BimEL expression. (
  • In addition, TCR stimulation results in up-regulation of Bcl-x L to enhance T cell survival intrinsically. (
  • Thus, the PKC-θ-mediated signals may function not only in the initial activation of naive CD4 + T cells, but also in their survival during T cell activation by regulating Bcl-x L levels through NF-κB and AP-1 pathways. (
  • CD28, the costimulatory molecule, mediates the critical signals required for up-regulation of Bcl-x L during T cell activation ( 2 , 4 , 5 ). (
  • It was reported that distinct motifs within the cytoplasmic domain of CD28 regulate T cell proliferation and induction of Bcl-x L ( 7 ), suggesting differential signals are responsible for these two CD28-regulated biological effects. (
  • Akt, a target of PI3K, has been shown to mediate T cell survival by regulating Bcl-x L most likely via activation of NF-κB ( 9 ). (
  • Bcl-2 proteins, cell migration and embryonic development: lessons from zebrafish. (
  • Within minutes following the incidence of an ischemic stroke, necrotic cell death is initiated in the core region of the infarct. (
  • These results suggest that MP selectively inhibits oligodendrocyte but not neuronal cell death via a receptor-mediated action and may be a mechanism for its limited protective effect after SCI. (
  • Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. (
  • citation needed] Cancer can be seen as a disturbance in the homeostatic balance between cell growth and cell death. (
  • Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. (
  • But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma. (
  • Other studies have shown that dendritic cell lifespan may be partly controlled by a timer dependent on anti-apoptotic Bcl-2. (
  • Life requires orchestrated control of cell proliferation, cell maintenance, and cell death. (
  • Involved in these decisions are protein complexes that assimilate a variety of inputs that report on the status of the cell and lead to an output response. (
  • The mechanism of mitochondrial damage, a key contributor to renal tubular cell death during acute kidney injury, remains largely unknown. (
  • In the present study we determined if p53-mediated neuronal cell death required caspase activation. (
  • Caspase inhibitors protected embryonic telencephalic neurons, but not postnatal cortical neurons, from DNA damage-induced cell death as measured by direct cell counting and annexin V staining. (
  • In marked contrast to the caspase inhibitors, an inhibitor of the DNA repair enzyme, poly(ADP-ribose) polymerase, conferred significant protection from genotoxic and excitotoxic cell death on postnatal cortical neurons but had no effect on embryonic neurons. (
  • Glutamate-mediated excitotoxicity in postnatal neurons was not associated with measurable changes in caspase activity, consistent with the failure of caspase inhibitors to prevent cell death under these conditions. (
  • Thus, p53-mediated neuronal cell death may occur via both caspase-dependent and caspase-independent pathways. (
  • However, the relative importance of caspase activation in neurons depends on the developmental status of the cell and the specific nature of the death stimulus. (
  • In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. (
  • The subsequent release of cytochrome c initiates cell death. (
  • In cell EPR of site-directed spin labelined proteins is an emerging area, which faces challenges in terms of sensitivity, selectivity and labels' lifetime. (
  • Cadmium induces caspase-mediated cell death: suppression by Bcl-2. (
  • Expression of Bcl-2 or CrmA each suppressed cadmium-induced cell death although Bcl-2 was somewhat more effective than CrmA. (
  • Both Asp-Glu-Val-Asp-aldehyde (DEVD-cho) and Tyr-Val-Ala-Asp-chloromethylketone (YVAD-cmk), selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. (
  • However, the nonselective caspase inhibitor, z-Val-Ala-Asp-floromethylketone (zVAD-fmk), was the most efficacious agent, almost completely blocking cadmium-induced cell death. (
  • The mechanisms leading to cell death after lactaptin treatment have not been well characterized. (
  • Expression of Bik but not mutant BikL61G induces and loss of Bik suppresses IFNγ-induced cell death in HAECs. (
  • These results demonstrate that IFNγ requires Bik to suppress nuclear localization of phospho-ERK1/2 to channel cell death in AECs. (
  • The decision between life and death may depend on possible costimuli or the cell type. (
  • Bik/Blk/Nbk was consistently induced by IFNγ, and its expression induced cell death. (
  • Loss of Bik but not p53, Bim, or Bax conferred resistance to IFNγ but not to thapsigargin-induced cell death. (
  • Primary mouse AECs (MAECs) from p53 - but not bik -deficient mice were protected from DNA damage-induced cell death. (
  • The process of apoptotic cell death is central to our understanding of normal development, homeostasis, and aging, as well as diseases such as cancer, neurodegeneration, ischemic injury, and AIDS. (
  • It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic). (
  • Bcl-x is a dominant regulator of programmed cell death in mammalian cells. (
  • The long form (Bcl-x(L), displays cell death repressor activity, but the short isoform (Bcl-x(S)) and the β-isoform (Bcl-xβ) promote cell death. (
  • Using a yeast autophagy reconstitution assay and two transfected mammalian cell systems, Bcl-2 was found to inhibit beclin 1-mediated formation of autophagic structures through a mechanism that required the functional binding sites mediating the interaction between these two proteins. (
  • The interaction between beclin 1 and Bcl-2 was confirmed in HT-29 cells overexpressing Bcl-2 by coimmmunoprecipitation, and beclin 1 was identified on endoplasmic and mitochondrial membranes (the locations of Bcl-2) based on cell fractionation and confocal microscopy. (
  • In addition, these cells were more susceptible to cell death under normal and starvation conditions. (
  • This cell death was inhibited by knockdown of the autophagy protein ATG5 by RNAi. (
  • Thus, Bcl-2 appears to be a more general inhibitor of cell death than previously appreciated. (
  • Using four M-phase specific chemotherapeutic agents, Bcl-XL and Bcl-2 provided similar protection against vincristine and vinblastine whereas Bcl-XL afforded as much as 50% greater cell viability than Bcl-2 against etoposide and teniposide-induced cell death. (
  • In addition, Bcl-XL provided significantly greater cell viability than Bcl-2 against methotrexate, fluorouracil, and hydroxyurea, three S-phase specific agents. (
  • These results indicate that Bcl-XL and Bcl-2 confer a differential ability to protect against chemotherapy-induced cell death, which appears to be dependent on the molecular mechanism targeted by the drug rather than its cell-cycle phase specificity. (
  • 2 Subsequently, Bcl-2 has been shown to repress cell death triggered by a diverse array of stimuli including chemotherapy and γ-irradiation. (
  • In the present studies, we transfected FL5.12 lymphoid cells with expression constructs that produce Flag-epitope tagged Bcl-2 and Bcl-XL and developed cell clones that express similar levels of these proteins as determined with a Flag-specific antibody. (
  • Our results show that Bcl-XL protected significantly better than Bcl-2 against cell death induced by several chemotherapy agents. (
  • In the study, published online today in Cell Reports , scientists found that inhibiting the action of a protein called BRD4 caused cancer cells to die in a mouse model of malignant peripheral nerve sheath tumors (MPNSTs). (
  • These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals. (
  • The functions of the BH3 proteins Bad and Bid are regulated by phosphorylation and proteolytic activation, respectively, in response to extrinsic cell survival/cell death stimuli ( 6 - 8 ). (
  • The cells obtain mutations in key cellular proteins that allow the developing cancer to grow, although breaking certain cellular rules, such as genomic instability, oncogene activation, loss of adhesion, along with breach of cell cycle checkpoints. (
  • We show here that PML overexpression induces rapid cell death, independent of de novo transcription and cell cycling. (
  • Arsenic enhances targeting of PML, BAX and p27KIP1 to NBs and synergizes with PML and IFN to induce cell death. (
  • Thus, cell death susceptibility correlates with NB recruitment of NB proteins. (
  • Dietary or adipocyte-derived free fatty acids (FFAs) contribute both to peripheral insulin resistance and to β-cell dysfunction and death in T2D. (
  • Chronic high-fat diet (HFD) leads to hyperglycemia as a consequence of impaired insulin secretion and insulin resistance ( 3 , 4 ), and in vitro exposure to saturated and, to a lesser extent, unsaturated FFAs induces β-cell dysfunction and death ( 5 , 6 ). (
  • Nonresolved ER stress induces cell death ( 11 , 12 ). (
  • The Gavathiotis laboratory aims to investigate mechanisms of protein-protein interactions in cell death and cell survival signaling, which are deregulated in cancer and other diseases. (
  • Programmed cell death is a genetically controlled physiological process that rids the body of unwanted or malfunctioning cells to maintain the normal development and homeostasis of multicellular organisms. (
  • Deregulation of cell death and cell survival programs leads to variety of disease conditions and understanding the molecular mechanisms that govern these signaling pathways is both fundamentally important and medically relevant. (
  • Using structural biology, biochemical, biophysical and cell biology studies, we aim to elucidate the mechanisms of protein-protein interactions and define the very determinants that modulate life and death decisions in healthy and malignant cells. (
  • We work towards a "chemical toolbox" of activators and inhibitors of major cell death and cell survival pathways to enable us to manipulate cell signaling and fate desicion in physiological and disease conditions and provide new research tools and future therapeutics. (
  • True or False: Cdk inhibitor proteins (CKI's) function primarily in the G1-S transition of the cell cycle. (
  • Antonawich, F.J. (2006) Palladium Lipoic Complex Utilizes Energy to Modulate Programmed Cell Death. (
  • Antonawich, F.J. (2006) Palladium Lipoic Complex (Poly MVA) Regulation of Cell Death. (
  • Antonawich, F.J. (2005) Poly MVA Induced Regulation of Cell Death in Cancer and Stroke. (
  • Antonawich, F.J. (2005) Poly MVA Provides Energy to Alter Cell Death. (
  • Antonawich, F.J. (2005) Poly MVA: Modulates Cancer Cell Death. (
  • Biochemical events lead to characteristic cell changes ( morphology ) and death. (
  • In 1885, anatomist Walther Flemming delivered a more precise description of the process of programmed cell death. (
  • What transformed cell death from obscurity to a major field of research were two things: the identification of components of the cell death control and effector mechanisms, and the linkage of abnormalities in cell death to human disease, in particular cancer. (
  • In H157 cell line, casticin increased expression of DR5 at protein levels but not affect the expression of DR4. (
  • Alberto R. Kornblihtt, a Howard Hughes Medical Institute international research scholar at the University of Buenos Aires and the National Research Council of Argentina, has found that UV radiation causes human cells to create proteins that trigger cell death. (
  • Kornblihtt and Muñoz found that, in both cases, UV radiation triggered production of the protein that encourages cell death. (
  • We demonstrated that the cell death mechanisms we found are independent of p53, " Kornblihtt says. (
  • The results of the study, "pRb2/p130 promotes radiation-induced death in glioblastoma cell line HJC12 by p73 upregulation and Bcl-2 downregulation," appear in the August 29 issue of Oncogene (Vol. 21, Issue 38). (
  • A novel angiogenic growth factor, hepatocyte growth factor (HGF), has been reported to inhibit endothelial cell death. (
  • Severe hypoxia increased the cell death rate in human aortic endothelial cells, whereas HGF significantly attenuated cell death. (
  • Overall, this study demonstrated that HGF prevented endothelial cell death induced by hypoxia through its antiapoptotic action. (
  • The antiapoptotic mechanisms of HGF in hypoxia-induced endothelial cell death largely depend on Bcl-2, but not Bcl-xL and Bax. (
  • On the other hand, proliferation and cell death are considered 2 mechanically related phenomena. (
  • However, a number of studies suggest that on activation, these receptors promote cell survival by (1) triggering specific signaling pathways, (2) modulating the activity of antiapoptotic molecules, and (3) inhibiting cell death effectors. (
  • 19 However, the mechanisms by which endothelial cell death is prevented by these angiogenic growth factors are largely unknown. (
  • Because the mechanisms responsible for their angiogenic activity remain enigmatic, we have addressed the following specific questions: (1) Does HGF have antiapoptotic actions on endothelial cell death induced by hypoxia? (
  • BCL-2 inhibitors BCL-2 is a protein inside of B cells that helps prevent cell death. (
  • RESEARCH DESIGN AND METHODS Islets isolated from mice lacking molecules implicated in cell death pathways were exposed to high concentrations of glucose or ribose. (
  • In addition, baicalein treatment increased B-cell lymphoma 2 (Bcl-2) and reduced Bax levels in the liver. (
  • Both Bcl-2 and Bax are proteins that regulate cell death. (
  • Based on these results, the researchers concluded that baicalein can effectively reduce liver injury induced by myocardial I/R by regulating cell death in the liver. (
  • Furthermore, the researchers found that the protective effect of baicalein against liver damage involves signaling pathways important for cell division, proliferation, and death. (
  • ABT-737 is a novel and potent Bcl-2 antagonist with single-agent activity against small-cell lung cancer (SCLC) cell lines. (
  • Relatively higher levels of Bcl-2, Bcl-X L , Bim and Noxa, and lower levels of Mcl-1 characterized naïve SCLC cell lines that were sensitive to ABT-737. (
  • Unlike other oncogenes, Bcl-2 promotes tumorigenesis by attenuating cell death as opposed to promoting cell proliferation ( 10 , 11 ). (
  • Studies have shown that Bcl-2 also plays a direct role in SCLC cell resistance to external apoptotic stimuli ( 8 , 9 , 29 , 30 ). (
  • The ultrasonic effect on cell disruption was revealed by increased concentrations of protein and carbohydrate released into the solution, and a decreased concentration of total suspended solids in cell suspension. (
  • Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third изд. (
  • Functional trade-offs in environmental tolerance may have occurred in parallel with the evolution of diversified pathways for the signaling of cell death in eukaryotic organisms. (
  • Unraveling the mechanisms by which organisms in extreme environments avoid cell death may suggest possible interventions during disease states and biostabilization of mammalian cells. (
  • Some animals like embryos of the brine shrimp, Artemia franciscana , exhibit profound metabolic depression and survive anoxia at room temperature for years ( Clegg, 1997 ) with no evidence of apoptotic or necrotic cell death. (
  • Survival presumably requires that unwanted initiation of cell death, in any of its various forms, is blunted or precluded. (
  • Current data do not permit a comprehensive evolutionary analysis of the regulation of cell death (cf. (
  • However, an emerging picture is that some regulatory systems for controlling cell death are more sensitive to energy disruption than others. (
  • is a type of cell-death. (
  • The effector phase eventually leads to cell death. (
  • 7) computational modeling of cell death. (
  • if more Bcl-xL is present, then pores are non-permeable to pro-apoptotic molecules and the cell survives. (
  • The formation of this complex was then believed to play a regulatory role in mammalian cell death. (
  • There are hidden routes for cell death as well, which are independent of APAF-1 and therefore the apoptosome. (
  • It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. (
  • It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. (
  • The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients. (
  • Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. (
  • Glutamate excitotoxicity is one of the most important mechanisms known to trigger cell death in CNS disorders. (
  • Because Ca2+ is a secondary messenger and regulates a large number of downstream processes, accumulation of Ca2+ causes improper regulation of these processes, eventually leading to cell death. (
  • Oxidative stress can directly cause neuron cell death or it can trigger a cascade of events that leads to protein misfolding, proteasomal malfunction, mitochondrial dysfunction, or glial cell activation. (
  • DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. (
  • Following mitochondrial dysfunction, the caspase cascade is activated ultimately leading to cell death. (
  • The mammalian bloodstream forms are notable for their cell surface proteins, variant surface glycoproteins, which undergo remarkable antigenic variation, enabling persistent evasion of host adaptive immunity leading to chronic infection. (
  • One of the main focuses of their cancer cell research is on cell proliferation and cell death. (
  • Dr. Cory's work has been published in many well-known research journals such as Blood (journal), The EMBO Journal, Nature (journal), Cell Death & Differentiation, and Proceedings of the National Academy of Sciences of the United States of America. (
  • Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. (
  • However, while overexpression of the other TMBIM proteins exhibit antiapoptotic effects by decreasing calcium ion concentrations, and thus preventing mitochondrial calcium ion overload, depolarization, ATP loss, reactive oxygen species production, cytochrome c release, and ultimately, cell death, overexpression of GHITM produces the opposite effect. (
  • This process involves a signal and interaction cascade of proteins leading to the engulfment and death of the targeted cell. (
  • CED-3 is the final protease in the interaction network and is responsible for activating the proteins involved in cell disassembly. (
  • When the cell receives an apoptotic signal via a receptor commonly referred to as a "death receptor", the protein EGL-1 is activated. (
  • The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. (
  • Necrosis-like cell death induced by BNIP3 may be related to this activity. (
  • Primary role of EpoR is to promote proliferation of erythroid progenitor cells and rescue erythroid progenitors from cell death. (
  • VDAC1 therefore allows for communication between the mitochondrion and the cell mediating the balance between cell metabolism and cell death. (
  • He showed that functional ced-3 and ced-4 genes were a prerequisite for cell death to be executed. (
  • transcription factors ces-1 and ces-2, and ced-8, which controls the timing of cell death. (
  • TNF, being an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells. (
  • Bok-P may be the cause for trophoblast cell death in pre-eclampsia, a dangerous pregnancy complication. (
  • Beclin-1 plays an important role in tumorigenesis, and neurodegeneration, being implicated in the autophagic programmed cell death. (
  • Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of the affected which causes diminished autophagy which in turn results in increased neuronal cell death. (
  • This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. (
  • In people with SLE and other autoimmune disorders this process is thought to be defective, causing either an increase in cell death and/or a decrease in the rate of dead cell clearance. (
  • These include increased levels of soluble Fas and bcl-2 and polymorphisms in the programmed cell death 1 and run-related transcription factor X1. (
  • More specifically, these molecules suppress the protein Bcl-2, which is a cancer-prone lymphoma protein, and induce cell death upon BRO (melanoma) cells. (
  • These interactions allow DLC1 to co-localize along with these proteins to focal adhesions at the periphery of the cell, where it is able to carry out its function as a Rho-GAP protein. (
  • FOXO1 upregulate Fas ligand (FasL) transcriptionally that result in promotes apoptotic cell death. (
  • Further, it was revealed that DNA damage-induced cell death in p53-deficient and p53-proficient cells reduced when human FOXO1 silenced by siRNA. (
  • BCL-6 genes are involved in several cell processes that can affect the ability of the B-cell to differentiate and proliferate. (
  • BCL-6 proteins repress genes involved in terminal differentiation and promote proliferation by blocking expression of a cell-cycle inhibitor (p27KIP1). (
  • A study of DLBCL cell lines indicated that 14-3-3ζ proteins may play a role in mediating resistance of DLBCL cells to CHOP. (
  • The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. (
  • This could lead to the disregulation of many signalling proteins and effectors within the cell, including RHEB. (
  • Ischemic cell death", or "Oncosis", is a form of accidental cell death. (
  • Oncosis refers to a series of cellular reactions following injury that precedes cell death. (
  • Stage two the reversibility threshold for the cell is passed and it becomes committed to cell death. (
  • The final stage is cell death and removal of the cell via phagocytosis mediated by an inflammatory response. (
  • Although ischemic cell death is the accepted name of the process, the alternative name of oncosis was introduced as the process involves the affected cell(s) swelling to an abnormally large size in known models. (
  • Oncosis: an important non-apoptotic mode of cell death. (
  • Programmed cell death (or PCD) is the death of a cell in any form, mediated by an intracellular program. (
  • Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. (
  • Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of programmed cell death. (
  • Autophagic or Type II cell-death. (
  • These cells are absent because they undergo programmed cell death - Horvitz: "Worms, Life and Death," 2002. (
  • Programmed cell death had been known long before "the worm people" began to publish their celebrated findings. (
  • In 1964 Richard A. Lockshin and Carroll Williams published their contribution on "Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths", where they used the concept of programmed cell death during a time when little research was being carried out on this topic. (
  • it is the usual method of eliminating organs and tissues that is useful only during embryonic or larval life Saunders and Lockshin reciprocally acknowledged that they benefited from each other's work, and both pointed out the possibility that cell death might be regulated. (
  • Their observations helped to lead later work toward the genetic pathways of programmed cell death. (
  • Giardia are flagellated protozoans that cause decreased expression of brush border enzymes, morphological changes to the microvillus, and programmed cell death of small intestinal epithelial cells. (
  • Following experimental elucidation of SMAC structure, small-molecule SMAC mimetics have been developed to mimic the tetrapeptide AVPI in the IAP binding domain of SMAC, which is responsible for binding the BIR3 domains in IAPs like XIAP, cIAP1, and cIAP2 to induce cell death, and sometimes, necroptosis. (
  • Some of the symptoms that result from cell death include loss of motor control, cognitive deterioration and autonomic nervous system dysfunction. (
  • Aβ was found to cause neurotoxicity and cell death in the brain when present in high concentrations. (
  • Aβ uses several routes in the central nervous system to cause cell death. (
  • This phosphorylation allows AKT to interact with BAD, a protein known to cause cell death. (
  • Thus an increase in Aβ results in an increase of the AKT/BAD complex, in turn stopping the action of the anti-apoptotic protein Bcl-2, which normally functions to stop cell death, causing accelerated neuron breakdown and the progression of AD. (
  • His laboratory also identified the roles of EBV Nuclear antigens (EBNAs) and Latent Infection Membrane Proteins (LMPs) in EBV mediated cell growth transformation. (
  • It is interesting to note that cell death is not prevented by caspase inhibitors, or by BCL-2 or p53 mutagenesis, indicating that the traditional apoptotic caspase cascade is not the ultimate cause of cell death. (
  • However, proteasome inhibition alone does not seem to be responsible for HAMLET-induced cell death, as proteasome inhibitors have been shown to reduce the cytotoxicity of HAMLET. (
  • This is in contrast to necrosis, which is non-programmed cell death that results from injury to the cell. (
  • Paraptosis has been found in some developmental and neurodegenerative cell deaths, as well as induced by several cancer drugs. (
  • The group used human insulin-like growth factor 1 receptor (IGF-1R) to stimulate cell death in 293T cells and mouse embryonic fibroblasts, observing distinct differences from other forms of cell death. (
  • While Sperandio was the first to publish the term paraptosis, this was not the first time cell death with the properties of paraptosis was observed. (
  • Terms such as "cytoplasmic" and "type 3 cell death" had previously been used to describe these forms of cell death. (
  • These forms are very similar to paraptosis morphologically, and it is possible that some instances of cell death originally described as one of these forms are occurrences of paraptosis. (
  • Paraptosis is a form of type III programmed cell death with a unique combination of certain apoptotic and necrotic characteristics. (
  • Instead, paraptosis displays a somewhat primitive cell death path, comparable to necrosis, including characteristic cytoplasmic vacuole formation and late mitochondrial swelling and clumping. (
  • While certain templates of programmed cell death have been known to rely on de novo protein synthesis, paraptotic cell death induced by IGFIR-IC in 293T cells is deterred by actinomycin D and cycloheximide, thus demonstrating a dependence on transcription and translation. (
  • Cell death induced by IGFIR-IC in 293T cells demonstrated cell death without associated caspase activity. (
  • The most defining difference observed (as of April 2014) between paraptosis and autophagic cell death (cell death type 2) is paraptosis' lack of the characteristic autophagic vacuoles seen in autophagic cell death. (
  • The caspase-9 then cleaves the proteins of the mitochondrial membrane, causing it to break down and start a chain reaction of protein denaturation and eventually phagocytosis of the cell. (
  • Certain isothiocyanates have also been shown to bind to the mutated p53 proteins found in many types of tumors, causing an increase in the rate of cell death. (
  • As a result, 14-3-3ζ functions to protect the cell from environmental stresses, such as chemotherapy-induced death, anoikis, growth factor deprivation, and hypoxia. (
  • CLU may promote tumorigenesis by facilitating BAX-KLU70 binding and, consequently, preventing BAX from localizing to the outer mitochondrial membrane to stimulate cell death. (
  • High affinity binding between proNGF, sortilin, and p75NTR can result in either survival or programmed cell death. (
  • The adenovirus E4orf4 is a viral protein with tumour-selective cell killing capabilities. (
  • Cell Death Differ 16, 890-898 (2009). (
  • It prevents cell death by binding to calcium, an ion that causes cell death. (
  • TCTP is a multifunctional and highly conserved protein that existed ubiquitously in different eukaryote species and distributed widely in various tissues and cell types. (
  • TCTP has properties of a tubulin binding protein that associates with microtubules in a cell cycle-dependent manner. (
  • Expressing TCTP in U2OS (Human Bone Osteosarcoma Epithelial Cells) protected them from cell death induced by etoposide over various concentrations and durations of exposure. (
  • Cell death was more common in females than males, especially among those older than 70 years of age. (
  • As indicated in these two cases, apoptotic cell death plays a critical role in the formation of sexually dimorphic nucleus, and the apoptotic cell number within SDN negatively correlates with the volume of SDN between different sexes. (
  • P11's involvement with the cytoskeleton may aid the transport of other proteins throughout the cell and to the cell membrane. (
  • P11 has been implicated in the transportation of proteins involved in mood regulation, nociception, and cell polarization. (
  • It is involved in the trafficking of proteins to the plasma membrane and can be expressed on the cell surface as a receptor. (
  • Many of the transported proteins are cell surface receptors in signal transduction pathways and ion channels. (
  • Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogen, the activated form of which plays an important role in regulating anticoagulation, inflammation, cell death, and maintaining the permeability of blood vessel walls in humans and other animals. (
  • This can occur with replication fork barriers, proteins such as PTIP, CHD4 and PARP1, which are normally cleared by the cell´s DNA damage sensors, surveyors, and responders BRCA1 and BRCA2. (
  • This can slow growth or result in programmed cell death of certain types of cancer cells. (
  • In most cell types, caspase-8 catalyzes the cleavage of the pro-apoptotic BH3-only protein Bid into its truncated form, tBid. (
  • The underlying mechanism by which safingol induces cell death is poorly understood. (
  • It is believed to exert a variety of inhibitory effects, resulting in a series of cascades that result in accidental necrotic cell death brought about by reactive oxygen species (ROS) and mediated by autophagy. (
  • Following autophagic activity, cell death is eventually induced by an as of yet unknown mechanism. (
  • Instead, several hallmarks of necrosis are observed, such as caspase-independent cell death, the loss of plasma membrane integrity, the collapse of mitochondrial membrane potential, and the depletion of intracellular ATP. (
  • Therefore, autophagy does not directly contribute to death, but is rather a failed attempt to preserve cell viability. (
  • The role of reactive oxygen species and autophagy in safingol-induced cell death. (
  • Cell death & disease, 2(3), e129. (
  • In particular, PPIA is predominantly expressed in the nucleus and cytoplasm of the cell, where it partakes in intracellular signaling, protein transport, and transcription regulation. (
  • This arrest leads to "shrinkage, blebbing, nuclear fragmentation, chromatin condensing" and other morphological changes that cause the cell to program death at this point. (
  • Hence, under normal cellular conditions, AIFM2 may promote cell survival rather than death by metabolic processes such as generating reactive oxygen species (ROS) to maintain survival signaling. (
  • The protein serves a protective function by binding to pathogens and also functions in a cell signaling capacity. (
  • In cellular biology, dependence receptors are proteins that mediate programmed cell death by monitoring the absence of certain trophic factors (or, equivalently, the presence of anti-trophic factors) that otherwise serve as ligands (interactors) for the dependence receptors. (
  • A trophic ligand is a molecule whose protein binding stimulates cell growth, differentiation, and/or survival. (
  • In addition, events such as cellular atrophy and process retraction may also be mediated by dependence receptors, although this has not been as well documented as the induction of programmed cell death. (
  • The term programmed cell death was first suggested by Lockshin & Williams in 1964. (
  • The dependence receptor notion was based on the observation that the effects of a number of receptors that function in both nervous system development and the production of tumors (especially metastasis) cannot be explained simply by a positive effect of signal transduction induced by ligand binding, but rather must also include cell death signaling in response to trophic withdrawal. (
  • This process is seen in developmental cell death, carcinogenesis (especially metastasis), neurodegeneration, and possibly non-lethal (sub-apoptotic) events such as neurite retraction and somal atrophy. (
  • conversely, in the absence of ligand, the receptors initiate and/or amplify a signal for programmed cell death. (
  • Mutation of the caspase site(s) in the receptor, of which there is typically one or two, prevents the trophic ligand withdrawal-induced programmed cell death. (
  • RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. (
  • However, the death-signaling pathways engaged after EGFR inhibition are poorly understood. (
  • It seems likely that many of these are resistant due to alterations in signaling pathways downstream of inhibition of EGFR activity, including whatever death-signaling and executing pathways are used. (
  • Among these, a variety of viruses code for proteins that specifically inhibit host apoptotic pathways to ensure maximal multiplication ( 1 ). (
  • In the present review, we examine the potential players in the death pathways, the current tools for examining these players and the models for studying neurological disease. (
  • A better understanding of the neuronal death pathways would provide targets for the development of therapeutic interventions for these diseases. (
  • It remains undetermined whether the survival of enteric neurons depends on extracellular survival signals in vivo and, if so, whether the absence of such factors results in the activation of conserved molecular and morphological death pathways. (
  • Resistance against TRAIL involves loss of TRAIL death receptors and/or activation of the MEK and/or Akt signal pathways. (
  • As such, paraptosis can be prevented by inhibiting specific protein kinases of these pathways. (
  • After activation and membrane insertion, we obtain intra-monomeric and inter-monomeric distances in the active oligomeric membrane-embedded conformation of the protein. (
  • Site-directed spin labeling EPR has been applied up to now to membrane proteins inserted in liposomes, membrane bilayers or nanodiscs. (
  • However, the molecular crowding and the lipid composition of each membrane differ tremendously, and may introduce additional still unknown triggering factors which modify the conformaional changes of the proteins under invetsigattion. (
  • Bcl-x(L) is 233 amino acyl residues (aas) long and exhibits a single very hydrophobic putative transmembrane α-helical segment (residues 210-226) when in the membrane. (
  • Irisin, a newly discovered myokine containing 111 amino acids with a molecular mass of 22 kDa, is released upon cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC5). (
  • The major facilitator superfamily (MFS) are membrane proteins which are expressed ubiquitously in all kingdoms of life for the import or export of target substrates. (
  • CED-9 also includes a transmembrane domain on the C-terminal end of the structure that anchors the protein to the mitochondrial membrane. (
  • Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. (
  • In addition, hydrolysis of PIP2 releases actin regulatory proteins assembled at PIP2 molecules on the membrane and allows them to promote the disassembly of actin filaments. (
  • The homodimer structure also facilitates SMAC-XIAP binding via the BIR2 domain, though it does not form until the protein is released into the cytoplasm as a result of outer mitochondrial membrane permeabilization. (
  • This major protein of the outer mitochondrial membrane of eukaryotes forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules. (
  • This protein contains about 280 amino acids and forms a beta barrel which spans the mitochondrial outer membrane. (
  • First, VDAC-1 represents a new structural class of outer membrane β-barrel proteins with an odd number of strands. (
  • This class of proteins has been implicated in the regulation of cytoskeleton assembly, cytosolic enzymes, and membrane dynamics. (
  • The VDAC2 protein belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. (
  • The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G protein-coupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. (
  • PI3K can also be activated by G protein-coupled receptors (GPCR), via G-protein βγ dimers or Ras which bind PI3K directly. (
  • CED-9 and Bcl-2 proved to be functional and structural homologs ( 8 ), and their survival function is opposed either by close relatives such as Bax ( 9 ) or by distant cousins such as mammalian Bik (also known as Nbk) ( 10 ) and nematode EGL-1 ( 11 ). (
  • Based on the relative affinities (IC 50 in nM) of ABT-737 for mammalian pro-survival proteins, determined in solution competition assays (), ABT-737 and Bad bind to the same subset of Bcl-2 pro-survival proteins. (
  • Here, we demonstrate that the mere inhibition of its synthesis by adenoviral transfer or classical transfection of antisense Hsp70 cDNA (asHsp70) results in massive death of human breast cancer cells (MDA-MB-468, MCF-7, BT-549, and SK-BR-3), whereas the survival of nontumorigenic breast epithelial cells (HBL-100) or fibroblasts (WI-38) is not affected. (
  • In the present report, we generated clones of FL5.12 lymphoid cells with similar levels of Bcl-2 and Bcl-XL using the Flag epitope to determine if these survival proteins could provide equivalent protection when challenged with chemotherapy or γ-irradiation. (
  • The regulation of neuronal survival and death by neurotrophic factors plays a central role in the sculpting of the nervous system, but the identity of survival signals for developing enteric neurons remains obscure. (
  • Such `life or death' decisions of neuronal survival are controlled in part by the availability of neurotrophic factors ( Yuan and Yankner, 2000 ). (
  • Previous developmental studies have delineated a number of unique features of the ENS with respect to neuronal survival and death. (
  • Because its activity is suppressed in the presence of survival-promoting proteins, this protein is suggested as a likely target for antiapoptotic proteins. (
  • This protein has also been shown as a requirement for heme production and in erythroid lineage, Bcl-xL is a major survival factor responsible for an estimated half of the total survival "signal" proerythroblasts must receive in order to survive and become red cells. (
  • This protein accumulates throughout the differentiation, ensuring the survival of erythroid progenitors. (
  • EpoR induced Jak2-Stat5 signaling, together with transcriptional factor GATA-1, induces the transcription of pro-survival protein Bcl-xL. (
  • Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail. (
  • described TCTP as a pro-survival protein by antagonizing BAX function This structure has a very complex topology composed of four beta-sheets and three alpha helices. (
  • Moreover, TCTP was described as a pro-survival protein antagonizing BAX function Sequence alignment of TCTP sequences from more than 30 different species reveals a high degree of conservation over a long period of evolution. (
  • Among the proteins involved in this response are nutrient-deprivation autophagy factor-1 (NAF-1)- and Bcl-2. (
  • NAF-1 is an important partner for Bcl-2 at the endoplasmic reticulum to functionally antagonize Beclin 1-dependent autophagy [Chang NC, Nguyen M, Germain M, Shore GC (2010) EMBO J 29(3):606- (
  • Macroautophagy, often referred to as autophagy, is a catabolic process that results in the autophagosomic-lysosomal degradation of bulk cytoplasmic contents, abnormal protein aggregates, and excess or damaged organelles. (
  • BH3 profiling reveals that mitochondrial BCL-2 is primed by death signals after EGFR inhibition in these cells. (
  • whereas premature death of normally long-lived cells may be the cause of certain degenerative disorders ( Barr and Tomei, 1994 ). (
  • In contrast, cells overexpressing Bcl-2 remained highly sensitive to ABT-737. (
  • Fig. S1 H1299 cells were transfected with EGFP-Bcl-2 for 48 h, and then the cells were fixed and subjected to immunofluorescent assay using anti-p62 (Enzo life) antibody to detect endogenous p62 ( red ) and DAPI to stain the nuclei ( blue ). (
  • To establish a vacuole that supports bacterial replication, Legionella pneumophila translocates a large number of bacterial proteins into host cells via the Dot/Icm type IV secretion system. (
  • Cells infected by L. pneumophila exhibited resistance to apoptotic stimuli, but the bacterial protein directly involved in this process remained elusive. (
  • DU145 cells overexpressing FAM3B protein were produced by lentiviral-mediated transduction of full-length FAM3B cDNA. (
  • Here, we characterized bcl-2 interactome by mass spectrometry in human lung adenocarcinoma cells. (
  • In contrast, human skin fibroblast CCL-116 and bovine primary fibroblast cells show resistances to KR and no significant changes in Bad, Bcl-X(L,) and cleaved PARP were observed. (
  • The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. (
  • The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. (
  • A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells. (
  • Under various stress conditions, the accumulation of the inducible Hsp70 enhances the ability of stressed cells to cope with increased concentrations of unfolded/denatured proteins ( 13 , 14 ). (
  • Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen. (
  • Lactaptin, the proteolytic fragment of human milk kappa-casein, induces the death of various cultured cancer cells. (
  • Knockdown of Bcl-2 in HeLa cells with siRNA resulted in an increase in the number of autophagic structures under starvation conditions compared with those observed in starved cells with wild-type levels of Bcl-2. (
  • This action caused another protein called BCL-2 to keep cancer cells from dying. (
  • To survive, cancer cells typically acquire changes enabling evasion of death signals. (
  • Cancer cells have a unique requirement to overcome death signaling engendered by these behaviors. (
  • Environmental factors such as diets rich in saturated fats contribute to dysfunction and death of pancreatic β-cells in diabetes. (
  • The apoptotic cells death was examined by flow cytometry using PI staining and DNA agarose gel electrophoresis. (
  • The researchers then repeated the experiments in cells missing a key protein called p53 . (
  • It attaches to a surface protein on cells called CD20. (
  • BCL-2 may build up in cancer cells and stop them from dying. (
  • Venetoclax is a BCL-2 inhibitor that allows the cancer cells to self-destruct. (
  • Conversely, a progressive decrease in the relative levels of Bcl-2 and Noxa and a progressive increase in Mcl-1 levels characterized the increased resistance of H146 cells following chronic exposure to ABT-737. (
  • Thus, SCLC cells sensitive to ABT-737 expressed the target proteins Bcl-2 and Bcl-X L , whereas Mcl-1 and factors regulating Mcl-1 function seem to contribute to the overall resistance of SCLC cells to ABT-737. (
  • Bcl-xL dysfunction in mice can cause ineffective production of red blood cells, severe anemia, hemolysis, and death. (
  • In cancerous mouse cells, those which contained Bcl-xL were able to survive while those that only expressed p53 died in a small period of time. (
  • Studies have shown that cells with p53 mutations have significantly lower levels of PUMA, making it a good candidate for a protein marker of p53 mutations, providing a simpler method for testing for p53 mutations. (
  • EpoR is a 52kDa peptide with a single carbohydrate chain resulting in a n approximately 56-57 kDa protein found on the surface of EPO responding cells. (
  • Serum amyloid P component is a protein that is thought to aid in the clearance of chromatin produced by apoptotic cells and deficiencies in this protein have been shown (in mice) to cause spontaneous formation of ANA. (
  • Upon release of nuclear proteins and chromatin, antigen presenting cells, such as dendritic cells and macrophages, display these antigens to T helper cells. (
  • Most normal germinal center B-cells express low levels of anti-apoptotic proteins such as Bcl-2. (
  • These proteins work with other transcription factors (BLIMP1, PAX5, XBP1) to form a regulatory circuit that controls the progression of germinal center B cells to plasma cells. (
  • HAMLET encodes the milk protein α-lactalbumin and is active against cancer cells only when complexed with oleic acid. (
  • The Mammalian translationally controlled tumour protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesised in cells during the early growth phase of some types of tumour, but which is also expressed in normal cells. (
  • The most successful targeted therapies are chemical entities that target or preferentially target a protein or enzyme that carries a mutation or other genetic alteration that is specific to cancer cells and not found in normal host tissue. (
  • The level of Bcl-2 in PD8 male rats is much higher than that in female rats of the same age, hence the number of apoptotic cells of MPNc in PD8 male rats is much lower than PD8 female rats. (
  • S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells. (
  • Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and leukocytes (white blood cells) that APC affects. (
  • Thus cells that express these proteins at sufficient concentrations manifest a state of dependence on their respective ligands. (
  • One of the promising approaches for the treatment or prevention of neurodegenerative diseases, including Parkinson's disease, is to investigate the molecular basis of neurodegeneration or neuronal death and elucidate possible therapeutic molecular targets. (
  • In the nervous system, aberrant neuronal death is an outstanding feature of neurodegenerative diseases. (
  • and neuronal death (Pike et al. (
  • These results suggest that physiological neuronal death may not take place during ENS development. (
  • This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein-dependent and β-arrestin-dependent signal transduction. (
  • Acute alcohol abuse causes damage to and functional impairment of several organs affecting protein, carbohydrate, and fat metabolism. (