A ubiquitously found basic protein that binds to phosphatidylethanolamine and NUCLEOTIDES. It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. Phosphatidylethanolamine-binding protein is the precursor of hippocampal cholinergic neurostimulating peptide, which is cleaved from the N-terminal region of the protein.
Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as SEX HORMONE-BINDING GLOBULIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
A cell line derived from cultured tumor cells.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
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.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
Agents that inhibit PROTEIN KINASES.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
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.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
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.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Transport proteins that carry specific substances in the blood or across cell membranes.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Established cell cultures that have the potential to propagate indefinitely.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
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.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p. (1/296)

In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MAPKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that is independent of Far1p, we constructed far1 CLN strains that undergo G1 arrest from increased activation of the mating MAP kinase pathway. We find that Fus3p and Kss1p both control G1 arrest through multiple functions that operate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mechanism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus3p and Kss1p counteract G1 arrest through overlapping and distinct functions. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly, Fus3p promotes proliferation by a novel function that is not linked to reduced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic analysis suggests that Fus3p promotes proliferation through activation of Mcm1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions that inhibit the Cdc28p machinery and proliferative functions that bypass this inhibition.  (+info)

Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. (2/296)

We have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces cerevisiae and have grown crystals using microseeding techniques. Phosphorylation of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the binary CDK2-cyclin A complex. Phosphorylated CDK2 exhibits histone H1 kinase activity corresponding to approximately 0.3% of that observed with the fully activated phosphorylated CDK2-cyclin A complex. Fluorescence measurements have shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. By contrast, phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. The structures are similar, with the major difference occurring in the activation segment, which is disordered in phosphorylated CDK2. The greater mobility of the activation segment in phosphorylated CDK2 and the absence of spontaneous crystallization suggest that phosphorylated CDK2 may adopt several different mobile states. The majority of these states are likely to correspond to inactive conformations, but a small fraction of phosphorylated CDK2 may be in an active conformation and hence explain the basal activity observed.  (+info)

A Cdc24p-Far1p-Gbetagamma protein complex required for yeast orientation during mating. (3/296)

Oriented cell growth requires the specification of a site for polarized growth and subsequent orientation of the cytoskeleton towards this site. During mating, haploid Saccharomyces cerevisiae cells orient their growth in response to a pheromone gradient overriding an internal landmark for polarized growth, the bud site. This response requires Cdc24p, Far1p, and a heterotrimeric G-protein. Here we show that a two- hybrid interaction between Cdc24p and Gbeta requires Far1p but not pheromone-dependent MAP-kinase signaling, indicating Far1p has a role in regulating the association of Cdc24p and Gbeta. Binding experiments demonstrate that Cdc24p, Far1p, and Gbeta form a complex in which pairwise interactions can occur in the absence of the third protein. Cdc24p localizes to sites of polarized growth suggesting that this complex is localized. In the absence of CDC24-FAR1-mediated chemotropism, a bud site selection protein, Bud1p/Rsr1p, is essential for morphological changes in response to pheromone. These results suggest that formation of a Cdc24p-Far1p-Gbetagamma complex functions as a landmark for orientation of the cytoskeleton during growth towards an external signal.  (+info)

Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. (4/296)

The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.  (+info)

Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. (5/296)

Exit from mitosis in budding yeast requires a group of essential proteins--including the GTPase Tem1 and the protein phosphatase Cdc14--that downregulate cyclin-dependent kinase activity. We identified a mutation, net1-1, that bypasses the lethality of tem1 delta. NET1 encodes a novel protein, and mass spectrometric analysis reveals that it is a key component of a multifunctional complex, denoted RENT (for regulator of nucleolar silencing and telophase), that also contains Cdc14 and the silencing regulator Sir2. From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. Nucleolar sequestration may be a general mechanism for the regulation of diverse biological processes.  (+info)

Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae. (6/296)

Saccharomyces cerevisiae proteins Cdc4 and Cdc20 contain WD40 repeats and participate in proteolytic processes. However, they are thought to act at two different stages of the cell cycle: Cdc4 is involved in the proteolysis of the Cdk inhibitor, Sic1, necessary for G(1)/S transition, while Cdc20 mediates anaphase-promoting complex-dependent degradation of anaphase inhibitor Pds1, a process necessary for the onset of chromosome segregation. We have isolated three mutant alleles of CDC4 (cdc4-10, cdc4-11, and cdc4-16) which suppress the nuclear division defect of cdc20-1 cells. However, the previously characterized mutation cdc4-1 and a new allele, cdc4-12, do not alleviate the defect of cdc20-1 cells. This genetic interaction suggests an additional role for Cdc4 in G(2)/M. Reexamination of the cdc4-1 mutant revealed that, in addition to being defective in the onset of S phase, it is also defective in G(2)/M transition when released from hydroxyurea-induced S-phase arrest. A second function for CDC4 in late S or G(2) phase was further confirmed by the observation that cells lacking the CDC4 gene are arrested both at G(1)/S and at G(2)/M. We subsequently isolated additional temperature-sensitive mutations in the CDC4 gene (such as cdc4-12) that render the mutant defective in both G(1)/S and G(2)/M transitions at the restrictive temperature. While the G(1)/S block in both cdc4-12 and cdc4Delta mutants is abolished by the deletion of the SIC1 gene (causing the mutants to be arrested predominantly in G(2)/M), the preanaphase arrest in the cdc4-12 mutant is relieved by the deletion of PDS1. Collectively, these observations suggest that, in addition to its involvement in the initiation of S phase, Cdc4 may also be required for the onset of anaphase.  (+info)

Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. (7/296)

The separation of sister chromatids in anaphase is followed by spindle disassembly and cytokinesis. These events are governed by the anaphase-promoting complex (APC), which triggers the ubiquitin-dependent proteolysis of key regulatory proteins: anaphase requires the destruction of the anaphase inhibitor Pds1, whereas mitotic exit requires the destruction of mitotic cyclins and the inactivation of Cdk1. We find that Pds1 is not only an inhibitor of anaphase, but also blocks cyclin destruction and mitotic exit by a mechanism independent of its effects on sister chromatid separation. Pds1 is also required for the mitotic arrest and inhibition of cyclin destruction that occurs after DNA damage. Even in anaphase cells, where Pds1 levels are normally low, DNA damage stabilizes Pds1 and prevents cyclin destruction and mitotic exit. Pds1 blocks cyclin destruction by inhibiting its binding partner Esp1. Mutations in ESP1 delay cyclin destruction; overexpression of ESP1 causes premature cyclin destruction in cells arrested in metaphase by spindle defects and in cells arrested in metaphase and anaphase by DNA damage. The effects of Esp1 are dependent on Cdc20 (an activating subunit of the APC) and on several additional proteins (Cdc5, Cdc14, Cdc15, Tem1) that form a regulatory network governing mitotic exit. We speculate that the inhibition of cyclin destruction by Pds1 may contribute to the ordering of late mitotic events by ensuring that mitotic exit is delayed until after anaphase is initiated. In addition, the stabilization of Pds1 after DNA damage provides a mechanism to delay both anaphase and mitotic exit while DNA repair occurs.  (+info)

SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. (8/296)

We have identified SGT1 as a dosage suppressor of skp1-4, a mutation causing defects in yeast kinetochore function. Sgt1p physically associates with Skp1p in vivo and in vitro. SGT1 is an essential gene, and different sgt1 conditional mutants arrest with either a G1 or G2 DNA content. Genetic and phenotypic analyses of sgt1-3 (G2 allele) mutants support an essential role in kinetochore function. Sgt1p is required for assembling the yeast kinetochore complex, CBF3, via activation of Ctf13p. Sgt1p also associates with SCF (Skp1p/Cdc53p/F box protein) ubiquitin ligase. sgt1-5 (G1 allele) mutants are defective in Sic1p turnover in vivo and Cln1p ubiquitination in vitro. Human SGT1 rescues an sgt1 null mutation, suggesting that the function of SGT1 is conserved in evolution.  (+info)

Phosphatidylethanolamine-binding protein (PEBP) is not a medical term per se, but rather a biochemical term. PEBP is a family of small proteins that bind to phosphatidylethanolamine (PE), a type of phospholipid found in the cell membrane. The function of PEBP is not entirely clear, but it's believed to be involved in various cellular processes such as signal transduction, regulation of enzyme activity, and apoptosis (programmed cell death).

There are several isoforms of PEBP, including Raf kinase inhibitor protein (RKIP), phosphatidylethanolamine-binding protein 1 (PEBP1), and neuronal PE-binding protein 1 (NPEBP1). Some of these isoforms have been implicated in various diseases, including cancer and neurological disorders. However, more research is needed to fully understand the role of PEBP in human health and disease.

Androgen-binding protein (ABP) is a protein that binds specifically to androgens, which are hormones such as testosterone that play a role in male sexual development and masculine characteristics. ABP is produced in the Sertoli cells of the testes and helps to regulate the levels of androgens within the testes by storing them and slowly releasing them over time. This is important for maintaining normal sperm production and male reproductive function.

ABP is also found in other tissues, including the prostate gland, where it may play a role in regulating the growth and development of this tissue. Abnormal levels of ABP have been associated with certain medical conditions, such as prostate cancer and infertility.

Cyclin-Dependent Kinase Inhibitor p27, also known as CDKN1B or p27Kip1, is a protein that regulates the cell cycle. It inhibits the activity of certain cyclin-dependent kinases (CDKs), which are enzymes that play key roles in regulating the progression of the cell cycle.

The cell cycle is a series of events that cells undergo as they grow and divide. Cyclins and CDKs help to control the different stages of the cell cycle by activating and deactivating various proteins at specific times. The p27 protein acts as a brake on the cell cycle, preventing cells from dividing too quickly or abnormally.

When p27 binds to a CDK-cyclin complex, it prevents the complex from phosphorylating its target proteins, which are necessary for the progression of the cell cycle. By inhibiting CDK activity, p27 helps to ensure that cells divide only when the proper conditions are met.

Mutations in the CDKN1B gene, which encodes p27, have been associated with several types of cancer, including breast, lung, and prostate cancer. These mutations can lead to decreased levels of p27 or impaired function, allowing cells to divide uncontrollably and form tumors.

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that play crucial roles in regulating the cell cycle, transcription, and other cellular processes. They are activated by binding to cyclin proteins, which accumulate and degrade at specific stages of the cell cycle. The activation of CDKs leads to phosphorylation of various downstream target proteins, resulting in the promotion or inhibition of different cell cycle events. Dysregulation of CDKs has been implicated in several human diseases, including cancer, and they are considered important targets for drug development.

Cyclin-dependent kinase inhibitor p21, also known as CDKN1A or p21/WAF1/CIP1, is a protein that regulates the cell cycle. It inhibits the activity of cyclin-dependent kinases (CDKs), which are enzymes that play crucial roles in controlling the progression of the cell cycle.

The binding of p21 to CDKs prevents the phosphorylation and activation of downstream targets, leading to cell cycle arrest. This protein is transcriptionally activated by tumor suppressor protein p53 in response to DNA damage or other stress signals, and it functions as an important mediator of p53-dependent growth arrest.

By inhibiting CDKs, p21 helps to ensure that cells do not proceed through the cell cycle until damaged DNA has been repaired, thereby preventing the propagation of potentially harmful mutations. Additionally, p21 has been implicated in other cellular processes such as apoptosis, differentiation, and senescence. Dysregulation of p21 has been associated with various human diseases, including cancer.

Cyclins are a family of regulatory proteins that play a crucial role in the cell cycle, which is the series of events that take place as a cell grows, divides, and produces two daughter cells. They are called cyclins because their levels fluctuate or cycle during the different stages of the cell cycle.

Cyclins function as subunits of serine/threonine protein kinase complexes, forming an active enzyme that adds phosphate groups to other proteins, thereby modifying their activity. This post-translational modification is a critical mechanism for controlling various cellular processes, including the regulation of the cell cycle.

There are several types of cyclins (A, B, D, and E), each of which is active during specific phases of the cell cycle:

1. Cyclin D: Expressed in the G1 phase, it helps to initiate the cell cycle by activating cyclin-dependent kinases (CDKs) that promote progression through the G1 restriction point.
2. Cyclin E: Active during late G1 and early S phases, it forms a complex with CDK2 to regulate the transition from G1 to S phase, where DNA replication occurs.
3. Cyclin A: Expressed in the S and G2 phases, it associates with both CDK2 and CDK1 to control the progression through the S and G2 phases and entry into mitosis (M phase).
4. Cyclin B: Active during late G2 and M phases, it partners with CDK1 to regulate the onset of mitosis by controlling the breakdown of the nuclear envelope, chromosome condensation, and spindle formation.

The activity of cyclins is tightly controlled through several mechanisms, including transcriptional regulation, protein degradation, and phosphorylation/dephosphorylation events. Dysregulation of cyclin expression or function can lead to uncontrolled cell growth and proliferation, which are hallmarks of cancer.

Cell cycle proteins are a group of regulatory proteins that control the progression of the cell cycle, which is the series of events that take place in a eukaryotic cell leading to its division and duplication. These proteins can be classified into several categories based on their functions during different stages of the cell cycle.

The major groups of cell cycle proteins include:

1. Cyclin-dependent kinases (CDKs): CDKs are serine/threonine protein kinases that regulate key transitions in the cell cycle. They require binding to a regulatory subunit called cyclin to become active. Different CDK-cyclin complexes are activated at different stages of the cell cycle.
2. Cyclins: Cyclins are a family of regulatory proteins that bind and activate CDKs. Their levels fluctuate throughout the cell cycle, with specific cyclins expressed during particular phases. For example, cyclin D is important for the G1 to S phase transition, while cyclin B is required for the G2 to M phase transition.
3. CDK inhibitors (CKIs): CKIs are regulatory proteins that bind to and inhibit CDKs, thereby preventing their activation. CKIs can be divided into two main families: the INK4 family and the Cip/Kip family. INK4 family members specifically inhibit CDK4 and CDK6, while Cip/Kip family members inhibit a broader range of CDKs.
4. Anaphase-promoting complex/cyclosome (APC/C): APC/C is an E3 ubiquitin ligase that targets specific proteins for degradation by the 26S proteasome. During the cell cycle, APC/C regulates the metaphase to anaphase transition and the exit from mitosis by targeting securin and cyclin B for degradation.
5. Other regulatory proteins: Several other proteins play crucial roles in regulating the cell cycle, such as p53, a transcription factor that responds to DNA damage and arrests the cell cycle, and the polo-like kinases (PLKs), which are involved in various aspects of mitosis.

Overall, cell cycle proteins work together to ensure the proper progression of the cell cycle, maintain genomic stability, and prevent uncontrolled cell growth, which can lead to cancer.

Cyclin-Dependent Kinase Inhibitor p16, also known as CDKN2A or INK4a, is a protein that regulates the cell cycle. It functions as an inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, which are enzymes that play a crucial role in regulating the progression of the cell cycle.

The p16 protein is produced in response to various signals, including DNA damage and oncogene activation, and its main function is to prevent the phosphorylation and activation of the retinoblastoma protein (pRb) by CDK4/6. When pRb is not phosphorylated, it binds to and inhibits the E2F transcription factor, which results in the suppression of genes required for cell cycle progression.

Therefore, p16 acts as a tumor suppressor protein by preventing the uncontrolled proliferation of cells that can lead to cancer. Mutations or deletions in the CDKN2A gene, which encodes the p16 protein, have been found in many types of human cancers, including lung, breast, and head and neck cancers.

The cell cycle is a series of events that take place in a cell leading to its division and duplication. It consists of four main phases: G1 phase, S phase, G2 phase, and M phase.

During the G1 phase, the cell grows in size and synthesizes mRNA and proteins in preparation for DNA replication. In the S phase, the cell's DNA is copied, resulting in two complete sets of chromosomes. During the G2 phase, the cell continues to grow and produces more proteins and organelles necessary for cell division.

The M phase is the final stage of the cell cycle and consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division). Mitosis results in two genetically identical daughter nuclei, while cytokinesis divides the cytoplasm and creates two separate daughter cells.

The cell cycle is regulated by various checkpoints that ensure the proper completion of each phase before progressing to the next. These checkpoints help prevent errors in DNA replication and division, which can lead to mutations and cancer.

Tumor suppressor proteins are a type of regulatory protein that helps control the cell cycle and prevent cells from dividing and growing in an uncontrolled manner. They work to inhibit tumor growth by preventing the formation of tumors or slowing down their progression. These proteins can repair damaged DNA, regulate gene expression, and initiate programmed cell death (apoptosis) if the damage is too severe for repair.

Mutations in tumor suppressor genes, which provide the code for these proteins, can lead to a decrease or loss of function in the resulting protein. This can result in uncontrolled cell growth and division, leading to the formation of tumors and cancer. Examples of tumor suppressor proteins include p53, Rb (retinoblastoma), and BRCA1/2.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

Medical Definition:
Microtubule-associated proteins (MAPs) are a diverse group of proteins that bind to microtubules, which are key components of the cytoskeleton in eukaryotic cells. MAPs play crucial roles in regulating microtubule dynamics and stability, as well as in mediating interactions between microtubules and other cellular structures. They can be classified into several categories based on their functions, including:

1. Microtubule stabilizers: These MAPs promote the assembly of microtubules and protect them from disassembly by enhancing their stability. Examples include tau proteins and MAP2.
2. Microtubule dynamics regulators: These MAPs modulate the rate of microtubule polymerization and depolymerization, allowing for dynamic reorganization of the cytoskeleton during cell division and other processes. Examples include stathmin and XMAP215.
3. Microtubule motor proteins: These MAPs use energy from ATP hydrolysis to move along microtubules, transporting various cargoes within the cell. Examples include kinesin and dynein.
4. Adapter proteins: These MAPs facilitate interactions between microtubules and other cellular structures, such as membranes, organelles, or signaling molecules. Examples include MAP4 and CLASPs.

Dysregulation of MAPs has been implicated in several diseases, including neurodegenerative disorders like Alzheimer's disease (where tau proteins form abnormal aggregates called neurofibrillary tangles) and cancer (where altered microtubule dynamics can contribute to uncontrolled cell division).

Proto-oncogene proteins c-RAF, also known as RAF kinases, are serine/threonine protein kinases that play crucial roles in regulating cell growth, differentiation, and survival. They are part of the RAS/RAF/MEK/ERK signaling pathway, which is a key intracellular signaling cascade that conveys signals from various extracellular stimuli, such as growth factors and hormones, to the nucleus.

The c-RAF protein exists in three isoforms: A-RAF, B-RAF, and C-RAF (also known as RAF-1). These isoforms share a common structure, consisting of several functional domains, including an N-terminal regulatory region, a central kinase domain, and a C-terminal autoinhibitory region. In their inactive state, c-RAF proteins are bound to the cell membrane through interactions with RAS GTPases and other regulatory proteins.

Upon activation of RAS GTPases by upstream signals, c-RAF becomes recruited to the plasma membrane, where it undergoes a conformational change that leads to its activation. Activated c-RAF then phosphorylates and activates MEK (MAPK/ERK kinase) proteins, which in turn phosphorylate and activate ERK (Extracellular Signal-Regulated Kinase) proteins. Activated ERK proteins can translocate to the nucleus and regulate the expression of various genes involved in cell growth, differentiation, and survival.

Mutations in c-RAF proto-oncogenes can lead to their constitutive activation, resulting in uncontrolled cell growth and division, which can contribute to the development of various types of cancer. In particular, B-RAF mutations have been identified in several human malignancies, including melanoma, colorectal cancer, and thyroid cancer.

Cyclin-dependent kinase inhibitor proteins (CDKIs) are a family of regulatory proteins that play a crucial role in the control of the cell cycle. They function by binding to and inhibiting the activity of cyclin-dependent kinases (CDKs), which are serine/threonine protein kinases that help drive the progression of the cell cycle.

There are two main families of CDKIs: the Ink4 family and the Cip/Kip family. The Ink4 family members, including p16INK4a, p15INK4b, p18INK4c, and p19INK4d, specifically inhibit CDK4 and CDK6, preventing their association with cyclin D and thus blocking the transition from G1 to S phase of the cell cycle. The Cip/Kip family members, including p21CIP1, p27KIP1, and p57KIP2, inhibit a broader range of CDKs, including CDK1, CDK2, CDK4, and CDK6, and can regulate multiple stages of the cell cycle.

CDKIs play important roles in various biological processes, such as cell growth, differentiation, and apoptosis. Dysregulation of CDKI function has been implicated in several human diseases, including cancer, where loss or mutation of CDKIs can lead to uncontrolled cell proliferation and tumorigenesis. Therefore, CDKIs are attractive targets for the development of anti-cancer therapies.

Cyclin-Dependent Kinase 2 (CDK2) is a type of enzyme that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. CDK2 is activated when it binds to a regulatory subunit called a cyclin.

During the cell cycle, CDK2 helps to control the progression from the G1 phase to the S phase, where DNA replication occurs. Specifically, CDK2 phosphorylates various target proteins that are involved in the regulation of DNA replication and the initiation of mitosis, which is the process of cell division.

CDK2 activity is tightly regulated through a variety of mechanisms, including phosphorylation, dephosphorylation, and protein degradation. Dysregulation of CDK2 activity has been implicated in various human diseases, including cancer. Therefore, CDK2 is an important target for the development of therapies aimed at treating these diseases.

Cyclin D1 is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells divide and grow. Specifically, Cyclin D1 is involved in the transition from the G1 phase to the S phase of the cell cycle. It does this by forming a complex with and acting as a regulatory subunit of cyclin-dependent kinase 4 (CDK4) or CDK6, which phosphorylates and inactivates the retinoblastoma protein (pRb). This allows the E2F transcription factors to be released and activate the transcription of genes required for DNA replication and cell cycle progression.

Overexpression of Cyclin D1 has been implicated in the development of various types of cancer, as it can lead to uncontrolled cell growth and division. Therefore, Cyclin D1 is an important target for cancer therapy, and inhibitors of CDK4/6 have been developed to treat certain types of cancer that overexpress Cyclin D1.

Cyclin A is a type of cyclin protein that regulates the progression of the cell cycle, particularly through the G1 and S phases. It forms a complex with and acts as a regulatory subunit for cyclin-dependent kinases (CDKs), specifically CDK2 and CDK1. The activation of Cyclin A-CDK complexes leads to phosphorylation of various target proteins, which in turn regulates DNA replication and the transition to mitosis.

Cyclin A levels rise during the late G1 phase and peak during the S phase, after which they decline rapidly during the G2 phase. Any abnormalities in Cyclin A regulation or expression can contribute to uncontrolled cell growth and cancer development.

Cyclin E is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, particularly during the G1 phase and the transition to the S phase. It functions as a regulatory subunit of the Cyclin-dependent kinase 2 (CDK2) complex, which is responsible for promoting the progression of the cell cycle.

Cyclin E is synthesized during the late G1 phase of the cell cycle and accumulates to high levels until it forms a complex with CDK2. The Cyclin E-CDK2 complex then phosphorylates several target proteins, leading to the activation of various downstream pathways that promote DNA replication and cell cycle progression.

The regulation of Cyclin E expression and activity is tightly controlled through multiple mechanisms, including transcriptional regulation, protein stability, and proteasomal degradation. Dysregulation of Cyclin E has been implicated in various human cancers, including breast, ovarian, and lung cancer, due to its role in promoting uncontrolled cell proliferation and genomic instability.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

Cyclin-Dependent Kinase 4 (CDK4) is a type of enzyme, specifically a serine/threonine protein kinase, that plays a crucial role in the regulation of the cell cycle. The cell cycle is the series of events that take place in a cell leading to its division and duplication. CDK4, when activated by binding to cyclin D, helps to promote the transition from the G1 phase to the S phase of the cell cycle. This transition is a critical point in the regulation of cell growth and division, and dysregulation of this process can lead to uncontrolled cell growth and cancer. CDK4 inhibitors are used in the treatment of certain types of cancer, such as breast and lung cancer, to block the activity of CDK4 and prevent tumor cell proliferation.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

CDC2 and CDC28 are members of the Serine/Threonine protein kinase family, which play crucial roles in the regulation of the cell cycle. These kinases were originally identified in yeast (CDC28) and humans (CDC2), but they are highly conserved across eukaryotes.

CDC2-CDC28 Kinases function as a part of larger complexes, often associated with cyclins, to control different phases of the cell cycle by phosphorylating specific substrates at key regulatory points. The activity of CDC2-CDC28 Kinases is tightly regulated through various mechanisms, including phosphorylation, dephosphorylation, and protein binding interactions.

During the G2 phase of the cell cycle, CDC2-CDC28 Kinases are inactivated by phosphorylation at specific residues (Tyr15 and Thr14). As the cell approaches mitosis, a family of phosphatases called Cdc25 removes these inhibitory phosphates, leading to activation of the kinase. Activated CDC2-CDC28 Kinases then initiate mitotic processes such as chromosome condensation and nuclear envelope breakdown.

In summary, CDC2-CDC28 Kinases are essential regulators of the eukaryotic cell cycle, controlling various aspects of cell division through phosphorylation of specific substrates. Their activity is tightly regulated to ensure proper progression through the cell cycle and prevent uncontrolled cell growth, which can lead to diseases such as cancer.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Cyclin-Dependent Kinase 5 (CDK5) is a type of protein kinase that plays crucial roles in the regulation of various cellular processes, particularly in neurons. Unlike other cyclin-dependent kinases, CDK5 is activated by associating with regulatory subunits called cyclins, specifically cyclin I and cyclin D1, but not during the cell cycle.

CDK5 activity is primarily involved in the development and functioning of the nervous system, where it regulates neuronal migration, differentiation, and synaptic plasticity. It has been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and various neurodevelopmental conditions.

CDK5 activity is tightly regulated by phosphorylation and interacting partners. Dysregulation of CDK5 can lead to abnormal neuronal function and contribute to the pathogenesis of neurological disorders.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Cyclin B is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. Cyclin B binds and activates cyclin-dependent kinase 1 (CDK1), forming the complex known as M-phase promoting factor (MPF). This complex triggers the events leading to cell division, such as chromosome condensation, nuclear envelope breakdown, and spindle formation. The levels of cyclin B increase during the G2 phase and are degraded by the anaphase-promoting complex/cyclosome (APC/C) at the onset of anaphase, allowing the cell cycle to progress into the next phase.

Cyclin C is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. Specifically, Cyclin C is involved in the transition from the G1 phase to the S phase of the cell cycle, during which DNA replication occurs.

Cyclin C forms a complex with cyclin-dependent kinase 8 (CDK8) and other regulatory subunits to form the CDK8 module, which is part of the mediator complex that regulates gene transcription. The activity of Cyclin C/CDK8 is regulated by various mechanisms, including phosphorylation and degradation, to ensure proper control of the cell cycle and prevent uncontrolled cell growth and division.

Mutations in the gene encoding Cyclin C have been associated with certain types of cancer, highlighting its importance in maintaining genomic stability and preventing tumorigenesis.

The G1 phase, or Gap 1 phase, is the first phase of the cell cycle, during which the cell grows in size and synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. During this phase, the cell also checks its growth and makes sure that it is large enough to proceed through the cell cycle. If the cell is not large enough, it will arrest in the G1 phase until it has grown sufficiently. The G1 phase is followed by the S phase, during which DNA replication occurs.

CDC2 protein kinase, also known as cell division cycle 2 or CDK1, is a type of enzyme that plays a crucial role in the regulation of the cell cycle. The cell cycle is the series of events that cells undergo as they grow, replicate their DNA, and divide into two daughter cells.

CDC2 protein kinase is a member of the cyclin-dependent kinase (CDK) family, which are serine/threonine protein kinases that are activated by binding to regulatory subunits called cyclins. CDC2 protein kinase is primarily associated with the regulation of the G2 phase and the entry into mitosis, the stage of the cell cycle where nuclear and cytoplasmic division occur.

CDC2 protein kinase functions by phosphorylating various target proteins, which alters their activity and contributes to the coordination of the different events that occur during the cell cycle. The activity of CDC2 protein kinase is tightly regulated through a variety of mechanisms, including phosphorylation and dephosphorylation, as well as the binding and destruction of cyclin subunits.

Dysregulation of CDC2 protein kinase has been implicated in various human diseases, including cancer, where uncontrolled cell division can lead to the formation of tumors. Therefore, understanding the regulation and function of CDC2 protein kinase is an important area of research in molecular biology and medicine.

Cyclin D is a type of cyclin protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. Specifically, Cyclin D is involved in the G1 phase of the cell cycle and works in conjunction with its partner enzyme, cyclin-dependent kinase 4 (CDK4) or CDK6, to phosphorylate and regulate the activity of several key proteins that control the transition from G1 to S phase.

There are several different types of Cyclin D proteins, including Cyclin D1, Cyclin D2, and Cyclin D3, which are encoded by different genes but share similar structures and functions. Overexpression or dysregulation of Cyclin D has been implicated in the development of various human cancers, as it can lead to uncontrolled cell growth and division. Therefore, understanding the role of Cyclin D in the cell cycle and its regulation is important for developing potential cancer therapies.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Cyclin-dependent kinase inhibitor p57, also known as CDKN1C or p57KIP2, is a protein that regulates the cell cycle and acts as a tumor suppressor. It inhibits the activity of cyclin-dependent kinases (CDKs), which are enzymes that play crucial roles in regulating the cell cycle and transitioning from one phase to another.

The p57 protein is encoded by the CDKN1C gene, which is located on chromosome 11p15.5. This region is known as an imprinted gene cluster, meaning that only one copy of the gene is active, depending on whether it is inherited from the mother or father. In the case of p57, the paternal allele is usually silenced, and only the maternal allele is expressed.

Mutations in the CDKN1C gene can lead to several developmental disorders, including Beckwith-Wiedemann syndrome (BWS), a condition characterized by overgrowth, abdominal wall defects, and an increased risk of childhood tumors. Loss of function mutations in CDKN1C have also been associated with an increased risk of cancer, particularly Wilms' tumor, a type of kidney cancer that typically affects children.

In summary, cyclin-dependent kinase inhibitor p57 is a protein that regulates the cell cycle and acts as a tumor suppressor by inhibiting the activity of CDKs. Mutations in the CDKN1C gene can lead to developmental disorders and an increased risk of cancer.

Cyclin D3 is a type of cyclin protein that regulates the cell cycle, particularly during the G1 phase. It forms a complex with and acts as a regulatory subunit of CDK4 or CDK6, which are cyclin-dependent kinases. This complex plays a crucial role in phosphorylating and inactivating the retinoblastoma protein (pRb), leading to the release of E2F transcription factors that promote the expression of genes required for DNA replication and cell cycle progression into the S phase.

Cyclin D3 is primarily expressed in activated lymphocytes and is essential for normal immune function, as well as in certain tissues during development. Alterations in CYCLIN D3 gene expression or function have been implicated in several types of cancer, such as leukemias and lymphomas, due to their role in uncontrolled cell proliferation.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Retinoblastoma Protein (pRb or RB1) is a tumor suppressor protein that plays a critical role in regulating the cell cycle and preventing uncontrolled cell growth. It is encoded by the RB1 gene, located on chromosome 13. The retinoblastoma protein functions as a regulatory checkpoint in the cell cycle, preventing cells from progressing into the S phase (DNA synthesis phase) until certain conditions are met.

When pRb is in its active state, it binds to and inhibits the activity of E2F transcription factors, which promote the expression of genes required for DNA replication and cell cycle progression. Phosphorylation of pRb by cyclin-dependent kinases (CDKs) leads to the release of E2F factors, allowing them to activate their target genes and drive the cell into S phase.

Mutations in the RB1 gene can result in the production of a nonfunctional or reduced amount of pRb protein, leading to uncontrolled cell growth and an increased risk of developing retinoblastoma, a rare form of eye cancer, as well as other types of tumors.

Cyclin B1 is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 1 (CDK1), also known as CDC2. During the G2 phase, Cyclin B1 levels accumulate and upon reaching a certain threshold, it binds to CDK1 to form the maturation promoting factor (MPF). The activation of MPF triggers the onset of mitosis by promoting nuclear envelope breakdown, chromosome condensation, and other events required for cell division. After the completion of mitosis, Cyclin B1 is degraded by the ubiquitin-proteasome system, allowing the cell cycle to progress back into G1 phase.

Cyclin-Dependent Kinase 6 (CDK6) is a type of enzyme known as a protein kinase, which adds phosphate groups to other proteins in the cell. CDK6 is primarily involved in regulating the cell cycle, the process by which cells divide and grow.

CDK6 functions by binding to cyclin proteins, forming active complexes that help drive the progression of the cell cycle from one phase to the next. Specifically, CDK6 plays a crucial role in the transition from the G1 phase to the S phase of the cell cycle, where DNA replication occurs.

CDK6 activity is tightly regulated by various mechanisms, including phosphorylation and dephosphorylation, as well as by binding to inhibitory proteins such as p16INK4a and p21CIP1. Dysregulation of CDK6 has been implicated in the development of several types of cancer, making it a potential target for cancer therapy.

In the context of cell biology, "S phase" refers to the part of the cell cycle during which DNA replication occurs. The "S" stands for synthesis, reflecting the active DNA synthesis that takes place during this phase. It is preceded by G1 phase (gap 1) and followed by G2 phase (gap 2), with mitosis (M phase) being the final stage of the cell cycle.

During S phase, the cell's DNA content effectively doubles as each chromosome is replicated to ensure that the two resulting daughter cells will have the same genetic material as the parent cell. This process is carefully regulated and coordinated with other events in the cell cycle to maintain genomic stability.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Cyclin D2 is a type of cyclin protein that regulates the cell cycle, particularly in the G1 phase. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 4 (CDK4) or CDK6, promoting the transition from G1 to S phase of the cell cycle. The expression of cyclin D2 is regulated by various growth factors, hormones, and oncogenes, and its dysregulation has been implicated in the development of several types of cancer.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Cyclin A1 is a type of cyclin protein that regulates the cell cycle, particularly during the S and G2 phases. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 2 (CDK2), helping to control the transition from the G1 phase to the S phase and from the S phase to the G2 phase. Cyclin A1 is expressed in various tissues, including ovary, testis, bone marrow, and lymphoid cells. Overexpression or dysregulation of cyclin A1 has been implicated in several types of cancer, making it a potential target for cancer therapy.

Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.

When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.

Examples of proto-oncogene proteins include:

1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.

Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.

Purines are heterocyclic aromatic organic compounds that consist of a pyrimidine ring fused to an imidazole ring. They are fundamental components of nucleotides, which are the building blocks of DNA and RNA. In the body, purines can be synthesized endogenously or obtained through dietary sources such as meat, seafood, and certain vegetables.

Once purines are metabolized, they are broken down into uric acid, which is excreted by the kidneys. Elevated levels of uric acid in the body can lead to the formation of uric acid crystals, resulting in conditions such as gout or kidney stones. Therefore, maintaining a balanced intake of purine-rich foods and ensuring proper kidney function are essential for overall health.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

E2F1 is a member of the E2F family of transcription factors, which are involved in the regulation of cell cycle progression and apoptosis (programmed cell death). Specifically, E2F1 plays a role as a transcriptional activator, binding to specific DNA sequences and promoting the expression of genes required for the G1/S transition of the cell cycle.

In more detail, E2F1 forms a complex with a retinoblastoma protein (pRb) in the G0 and early G1 phases of the cell cycle. When pRb is phosphorylated by cyclin-dependent kinases during the late G1 phase, E2F1 is released and can then bind to its target DNA sequences and activate transcription of genes involved in DNA replication and cell cycle progression.

However, if E2F1 is overexpressed or activated inappropriately, it can also promote apoptosis, making it a key player in both cell proliferation and cell death pathways. Dysregulation of E2F1 has been implicated in the development of various human cancers, including breast, lung, and prostate cancer.

Tumor suppressor protein p53, also known as p53 or tumor protein p53, is a nuclear phosphoprotein that plays a crucial role in preventing cancer development and maintaining genomic stability. It does so by regulating the cell cycle and acting as a transcription factor for various genes involved in apoptosis (programmed cell death), DNA repair, and cell senescence (permanent cell growth arrest).

In response to cellular stress, such as DNA damage or oncogene activation, p53 becomes activated and accumulates in the nucleus. Activated p53 can then bind to specific DNA sequences and promote the transcription of target genes that help prevent the proliferation of potentially cancerous cells. These targets include genes involved in cell cycle arrest (e.g., CDKN1A/p21), apoptosis (e.g., BAX, PUMA), and DNA repair (e.g., GADD45).

Mutations in the TP53 gene, which encodes p53, are among the most common genetic alterations found in human cancers. These mutations often lead to a loss or reduction of p53's tumor suppressive functions, allowing cancer cells to proliferate uncontrollably and evade apoptosis. As a result, p53 has been referred to as "the guardian of the genome" due to its essential role in preventing tumorigenesis.

Cyclin A2 is a type of cyclin protein that regulates the cell cycle, which is the series of events that cells undergo as they grow and divide. Specifically, Cyclin A2 plays a role in the progression from the G1 phase to the S phase (DNA synthesis phase) and from the G2 phase to the M phase (mitosis phase) of the cell cycle. It does this by binding to and activating cyclin-dependent kinases (CDKs), which are enzymes that help regulate the cell cycle.

Cyclin A2 is expressed at various points during the cell cycle, but its levels peak during the S and G2 phases. The protein is degraded during mitosis, ensuring that it is not present in excess during the next cell cycle. Dysregulation of Cyclin A2 has been implicated in the development of cancer, as uncontrolled cell growth and division are hallmarks of this disease.

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

Cyclin G is a type of protein that belongs to the cyclin family, which are involved in the regulation of the cell cycle. The human Cyclin G gene encodes two isoforms, Cyclin G1 and Cyclin G2, which share a similar structure but have different functions.

Cyclin G1 is known to play a role in the negative regulation of the cell cycle, particularly during the G1 phase. It interacts with several proteins, including CDKs (cyclin-dependent kinases), to regulate the activity of various transcription factors and other signaling pathways that control cell growth and division.

Cyclin G2, on the other hand, has been implicated in the regulation of DNA damage response and apoptosis (programmed cell death). It interacts with CDKs and other proteins to modulate the activity of various signaling pathways involved in these processes.

Overall, Cyclin G plays important roles in regulating cell cycle progression, DNA damage response, and apoptosis, and its dysregulation has been linked to several human diseases, including cancer.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Mitosis is a type of cell division in which the genetic material of a single cell, called the mother cell, is equally distributed into two identical daughter cells. It's a fundamental process that occurs in multicellular organisms for growth, maintenance, and repair, as well as in unicellular organisms for reproduction.

The process of mitosis can be broken down into several stages: prophase, prometaphase, metaphase, anaphase, and telophase. During prophase, the chromosomes condense and become visible, and the nuclear envelope breaks down. In prometaphase, the nuclear membrane is completely disassembled, and the mitotic spindle fibers attach to the chromosomes at their centromeres.

During metaphase, the chromosomes align at the metaphase plate, an imaginary line equidistant from the two spindle poles. In anaphase, sister chromatids are pulled apart by the spindle fibers and move toward opposite poles of the cell. Finally, in telophase, new nuclear envelopes form around each set of chromosomes, and the chromosomes decondense and become less visible.

Mitosis is followed by cytokinesis, a process that divides the cytoplasm of the mother cell into two separate daughter cells. The result of mitosis and cytokinesis is two genetically identical cells, each with the same number and kind of chromosomes as the original parent cell.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Cyclin G1 is a type of protein that belongs to the cyclin family, which are involved in the regulation of the cell cycle. The cell cycle is the series of events that take place as a cell grows, copies its DNA, and divides into two daughter cells.

Cyclin G1 regulates the cell cycle by interacting with various cyclin-dependent kinases (CDKs), which are enzymes that help control the progression of the cell cycle. Specifically, Cyclin G1 has been shown to inhibit the activity of CDK1 and CDK2, which play important roles in regulating the transition from the G1 phase to the S phase of the cell cycle.

Cyclin G1 has also been implicated in other cellular processes, including DNA damage repair, apoptosis (programmed cell death), and tumor suppression. Dysregulation of Cyclin G1 has been linked to various types of cancer, making it a potential target for cancer therapy.

Transcription factor DP1 (TFDP1) is not a specific medical term, but it is a term used in molecular biology and genetics. TFDP1 is a protein that functions as a transcription factor, which means it helps regulate the expression of genes by binding to specific DNA sequences and controlling the rate of transcription of those genes into messenger RNA (mRNA).

TFDP1 typically forms a complex with another transcription factor called E2F, and this complex plays a critical role in regulating the cell cycle and promoting cell division. TFDP1 can act as both a transcriptional activator and repressor, depending on which E2F family member it binds to and the specific context of the cell.

Mutations or dysregulation of TFDP1 have been implicated in various human diseases, including cancer. For example, overexpression of TFDP1 has been observed in several types of cancer, such as breast, lung, and prostate cancer, and is often associated with poor clinical outcomes. Therefore, understanding the role of TFDP1 in gene regulation and cellular processes may provide insights into the development of new therapeutic strategies for treating human diseases.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

The G2 phase, also known as the "gap 2 phase," is a stage in the cell cycle that occurs after DNA replication (S phase) and before cell division (mitosis). During this phase, the cell prepares for mitosis by completing the synthesis of proteins and organelles needed for chromosome separation. The cell also checks for any errors or damage to the DNA before entering mitosis. This phase is a critical point in the cell cycle where proper regulation ensures the faithful transmission of genetic information from one generation of cells to the next. If significant DNA damage is detected during G2, the cell may undergo programmed cell death (apoptosis) instead of dividing.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

E2F transcription factors are a family of proteins that play crucial roles in the regulation of the cell cycle, DNA repair, and apoptosis (programmed cell death). These factors bind to specific DNA sequences called E2F responsive elements, located in the promoter regions of target genes. They can act as either transcriptional activators or repressors, depending on which E2F family member is involved, the presence of co-factors, and the phase of the cell cycle.

The E2F family consists of eight members, divided into two groups based on their functions: activator E2Fs (E2F1, E2F2, and E2F3a) and repressor E2Fs (E2F3b, E2F4, E2F5, E2F6, and E2F7). Activator E2Fs promote the expression of genes required for cell cycle progression, DNA replication, and repair. Repressor E2Fs, on the other hand, inhibit the transcription of these same genes as well as genes involved in differentiation and apoptosis.

Dysregulation of E2F transcription factors has been implicated in various human diseases, including cancer. Overexpression or hyperactivation of activator E2Fs can lead to uncontrolled cell proliferation and tumorigenesis, while loss of function or inhibition of repressor E2Fs can result in impaired differentiation and increased susceptibility to malignancies. Therefore, understanding the roles and regulation of E2F transcription factors is essential for developing novel therapeutic strategies against cancer and other diseases associated with cell cycle dysregulation.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Proliferating Cell Nuclear Antigen (PCNA) is a protein that plays an essential role in the process of DNA replication and repair in eukaryotic cells. It functions as a cofactor for DNA polymerase delta, enhancing its activity during DNA synthesis. PCNA forms a sliding clamp around DNA, allowing it to move along the template and coordinate the actions of various enzymes involved in DNA metabolism.

PCNA is often used as a marker for cell proliferation because its levels increase in cells that are actively dividing or have been stimulated to enter the cell cycle. Immunostaining techniques can be used to detect PCNA and determine the proliferative status of tissues or cultures. In this context, 'proliferating' refers to the rapid multiplication of cells through cell division.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

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It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded ... CDKN1B has been shown to interact with: AKT1, CKS1B, Cyclin D3, Cyclin E1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4 ... "Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)". ... Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. ...
... notably the cyclin-dependent kinase inhibitor Sic1 - for ubiquitin-mediated protein degradation. CDC34 is required for ... CDC34 is a gene that in humans encodes the protein Ubiquitin-conjugating enzyme E2 R1. This protein is a member of the ... a novel protein that associates with serine/threonine kinase PRK1 in vivo". Gene. 256 (1-2): 113-21. doi:10.1016/S0378-1119(00) ... Semplici F, Meggio F, Pinna LA, Oliviero S (June 2002). "CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme ...
... can be induced by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor. In ... cultures by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor". Cell ... a cyclin-dependent kinase inhibitor, is dependent on p53 signaling". PLOS ONE. 8 (3): e59588. Bibcode:2013PLoSO...859588D. doi: ... Fu W, Ma L, Chu B, Wang X, Bui MM, Gemmer J, Altiok S, Pledger WJ (Jun 2011). "The cyclin-dependent kinase inhibitor SCH 727965 ...
... as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for ... and an F-box protein, which varies. Around 70 human F-box proteins have been identified. F-box proteins contain an F-box, which ... The ligases must simultaneously distinguish their protein substrate from thousands of other proteins in the cell, and from ... recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein ...
... serum amyloid A-activating factor 1 inhibits cell proliferation by the induction of cyclin-dependent protein kinase inhibitor ... Myc-associated zinc finger protein is a protein that in humans is encoded by the MAZ gene. MAZ (gene) has been shown to ... a myc-associated zinc finger protein, are regulated by casein kinase II". Biochem. Biophys. Res. Commun. 262 (1): 198-205. doi: ... protein interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity". Biochemistry ...
... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of ... "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi:10.1016/ ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ...
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... the CDKN2A gene which encodes cyclin-dependent kinase Inhibitor 2A, a protein that regulates cell proliferation and the CDKN2B ... This gene encodes CREB-binding protein, a protein that activates various transcription factors some of which are implicated in ... This gene encodes SET domain containing 2, a protein that acts to reduce the occurrence of gene deletions and tumor formation. ... TP53 encodes tumor suppressor p53, a protein that regulates cell proliferation, death, and tumor formation. Mutations in JAK- ...
Congenital insensitivity to pain Critical illness polyneuropathy CIP/KIP family of Cyclin-dependent kinase inhibitor proteins ...
... which leads to the increase in the synthesis of the selective cyclin-dependent kinase (CDK) inhibitor proteins, p12 and p16. ... The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. The ... Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a protein which in humans is encoded by the OGFR ... Retinoblastoma protein becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from ...
... cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdkn), pocket proteins of the retinoblastoma (Rb) family, ... hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in ... Rather, the Cyclin E/Cdk2 complex is constitutively active throughout the cycle, keeping retinoblastoma protein (pRb) ... while Cyclin E and Cdk2 are active during the late G1 phase and S phase; and Cyclin A and Cdk2 are active in the S phase and G2 ...
"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases". Cell. 75 (4): 805-16. doi:10.1016/ ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ... Cyclin-dependent kinase 2 has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ...
This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also ... Tomoda K, Kubota Y, Kato J (March 1999). "Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1". ... The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that ... April 1998). "A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits". ...
Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is ... This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6 ... "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to ... "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". Tu Q, Hao J, Zhou X, Yan L, Dai H, Sun B, et al ...
Inactivation of cyclin D is triggered by several cyclin-dependent kinase inhibitor protein (CKIs) like the INK4 family (e.g. ... Cyclins are eukaryotic proteins that form holoenzymes with cyclin-dependent protein kinases (Cdk), which they activate. The ... activate cyclin D gene in response to integrin. p27kip1 and p21cip1 are cyclin-dependent kinase inhibitors (CKIs) which ... two more cyclin D proteins have been identified. The three homologues, called cyclin D1, cyclin D2, and cyclin D3 are expressed ...
... are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology. 15 (5): 2672-81. doi: ... G1/S-specific cyclin-D2 is a protein that in humans is encoded by the CCND2 gene. The protein encoded by this gene belongs to ... Cyclins function as regulators of cyclin-dependent kinases. Different cyclins exhibit distinct expression and degradation ... "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular ...
... cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... p16 is also known as: p16INK4A p16Ink4 Cyclin-dependent kinase inhibitor 2A (CDKN2A) CDKN2 CDK 4 Inhibitor Multiple Tumor ... Hannon and David Beach discovered p16 in 1993 and correctly characterized the protein as a cyclin-dependent kinase inhibitor. ...
... (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C ... Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator ... "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, ... Lee MH, Reynisdóttir I, Massagué J (Mar 1995). "Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain ...
1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. ... "Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... 1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ...
CDKN2A is a tumour suppressor gene that encodes a tumor suppressor protein, p16 (cyclin-dependent kinase inhibitor 2A) and ... inhibits the kinase activity of the cyclin-dependent kinases CDK4 and CDK6, which in turn induce cell cycle arrest. p16 ... They bind to and inactivate the best known of these mechanisms, the tumor suppressor proteins p53 and retinoblastoma protein ... The pRb protein is inactivated by E7 in HPV+OPC, but in HPV-OPC it is the p16 tumour suppressor part of the pRb tumour ...
The transcription and half- life of cyclin-dependent kinase inhibitor p27KIP1 rises when FOXO1 is active. A study detects that ... Casein kinase 1, a growth factor-activated protein kinase, also phosphorylates and potentiates FOXO1 and translocates FOXO1 to ... repress cyclin D1 and cyclin D2 promoter activity and encourages cell cycle arrest at cyclin G1 (CCNG1). As a result of that, ... Guo S, Rena G, Cichy S, He X, Cohen P, Unterman T (June 1999). "Phosphorylation of serine 256 by protein kinase B disrupts ...
... a low-molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) - which has been localised to the p21 ... "CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". U.S. National Library of Medicine. Archived from ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... Eventual resistance to BRAF and MEK inhibitors may be due to a cell surface protein known as EphA2 which is now being ...
". "TP53 tumor protein p53 [Homo sapiens (human)] - Gene - NCBI". "CDKN2B cyclin dependent kinase inhibitor 2B [Homo sapiens ( ... both located at 9p21.3 and respectively encoding cyclin dependent kinase inhibitor 2A and cyclin dependent kinase inhibitor 2B ... In consequence, CCND1 overexpresses cyclin D1, a protein which promotes the cell cycle and thereby cellular proliferation. The ... a kinase that regulates the activity of various tumor suppressors and cell cycle proteins). It may also involve gains in the ...
The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and ... CDK inhibitors. The protein encoded by this gene is a member of the cyclin family and contains the cyclin box. The encoded ... "p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A". Mol. Cell. Biol. 16 (11): 6593-602. ... "Cyclin G1 and cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell cycle-regulated expression ...
The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and ... CDK inhibitors. The 8 species of cyclins reported in mammals, cyclins A through H, share a conserved amino acid sequence of ... Unlike cyclin G1, cyclin G2 contains a C-terminal PEST protein destabilization motif, suggesting that cyclin G2 expression is ... The amino acid sequence of cyclin G is well conserved among mammals. The nucleotide sequence of cyclin G1 and cyclin G2 are 53 ...
The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF ... The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF ... The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF ... The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF ...
Cks1 and Cks2 are adaptor-like proteins that bind many cyclin-dependent kinases. Cks1 and Cks2 are adaptor-like proteins that ... bind many cyclin-dependent kinases (Cdks). providers. Here we demonstrate malignancy PRT 062070 cells that overexpress Cks1 or ... 062070 PRT 062070 which mediates the ubiquitin-dependent proteolysis PRT 062070 of Cdk inhibitors p27 p21 and Rb family protein ... The protein expressions of Nox4 and SOD\1 were down regulated in C3H as with CBS+/?/C3H compared to CBS+/? mice ...
This protein belongs to the CDKN2 cyclin-dependent kinase inhibitor family. p16 comprises four ankyrin repeats, each spanning a ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ... p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ...
CDKN1C, or cyclin-dependent kinase inhibitor 1C, is a gene that encodes a protein implicated in cell cycle regulation. KCNQ1OT1 ... is a paternally expressed protein-coding gene. IGF2 is highly active during fetal development and acts as a growth promoter. ... or potassium voltage-gated channel subfamily Q member 1 opposite transcript 1 is the antisense transcript of the protein-coding ...
Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients. ... Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed ... 9. Roskoski R, Cyclin-dependent protein serine/threonine kinase inhibitors as anticancer drugs: Pharmacol Res, 2019; 139; 471- ... Cyclin B1 (CCNB1) and cyclin B2 (CCNB2) can form complexes with CDK1 (cyclin-dependent kinase 1) to regulate the G2/M phases of ...
... cyclin-dependent kinase inhibitor 1B (p27), octamer-binding transcription factor 3/4 (Oct3/4), and ,i,β,/i, catenin gene ... S phase kinase associated protein-2 (Skp2), cyclin-dependent kinase inhibitor 1B (p27), octamer-binding transcription factor 3/ ... Association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival," ... which promotes the ubiquitination-associated degradation of a cyclin-dependent kinase inhibitor p27, and increases NSCLC growth ...
Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.624.776.355]. *Cyclin-Dependent Kinase Inhibitor p19 [D12.776.624.776. ... "Cyclin-Dependent Kinase Inhibitor p19" by people in UAMS Profiles by year, and whether "Cyclin-Dependent Kinase Inhibitor p19" ... Cyclin-Dependent Kinase Inhibitor p19*Cyclin-Dependent Kinase Inhibitor p19. *Cyclin Dependent Kinase Inhibitor p19 ... An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. Aberrant expression of this protein has been ...
... cyclin-dependent kinase inhibitor 2A) and BAP1 (BRCA1 associated protein-1). These changes prevent the genes from doing their ...
The genetic changes and mechanisms underlying the progression of estrogen-dependent breast cancers to estrogen-independent, ... Mutant Proteins * Cyclin-Dependent Kinase Inhibitor p27 Grants and funding * CA84208/CA/NCI NIH HHS/United States ... We found that T47D cells contain only one p27kip1 (p27) allele coding for the p27 cyclin-dependent kinase (CDK) inhibitor. An ... Cyclin-Dependent Kinase Inhibitor p27 / genetics * Cyclin-Dependent Kinase Inhibitor p27 / physiology* ...
Treatment of thyroid cancer cells with VPA resulted in an increase in protein levels of the cyclin-dependent kinase inhibitors ... A, treatment of FTC236 cells with VPA resulted in a dose-dependent increase of the cyclin-dependent kinase inhibitors p21, p15 ... A, treatment of FTC236 cells with VPA resulted in a dose-dependent increase of the cyclin-dependent kinase inhibitors p21, p15 ... p21 is a universal inhibitor of cyclin-dependent kinases. The observations of up-regulation of p21 and down-regulation of ...
The p16 (p16INK4A) protein is a cyclin-dependent kinase (CDK) inhibitor that plays an important regulatory role in the cell ... By controlling the transition between the G1 and S phases through regulation of retinoblastoma protein, p16 decelerates ...
... stabilizes and activates the p53 protein.. The p53 protein activates the transcription of cyclin-dependent kinase inhibitor, ... Also, phosphorylation of p53 at multiple loci, by the ATM kinase and by other kinases activated by the ATM kinase, ... Inactivation of Cyclin E:Cdk2 complexes by p27/p21 (Homo sapiens) * Inactivation of Cyclin A:Cdk2 complexes by p27/p21 (Homo ... p53-Dependent G1/S DNA damage checkpoint (Homo sapiens) * p53-Dependent G1 DNA Damage Response (Homo sapiens) ...
... and biological evaluation of indolin-2-one derivatives as novel cyclin-dependent protein kinase 8 (CDK8) inhibitors. Hsu, J. Y. ... Design, synthesis, and biological activity of dual monoamine oxidase A and heat shock protein 90 inhibitors, N- ... buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors. Nalinratana, N., Suriya, U., ... Erratum: N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 ( ...
... of the ubiquitin ligase protein degradation pathway responsive for degrading the cell cycle cyclin dependent kinase inhibitor ... The second major emphasis of his laboratory relates to the functional properties of the precursor protein for IL-16, Pro-IL-16 ... It inhibits the cell cycle by acting as a scaffolding protein that assembles a histone deacetylase complex targeted via binding ...
"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases," Cell, 75:805-16, 1993. 3 G. Gyapay ... Perhaps the protein is an enzyme for which the catalytic mechanism has not yet been determined. Or maybe the compound is a ... Hidden amid a compendium of compounds in a crude cell extract is a protein that researchers have sought since its gene was ...
Loss of expression of the cyclin-dependent kinase inhibitor p27 through enhanced protein degradation frequently occurs in human ... Loss of expression of the cyclin-dependent kinase inhibitor p27 through enhanced protein degradation frequently occurs in human ... Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer.. G. CHIAPPETTA;DE MARCO, CARMELA;A. QUINTIERO;D. ... Degradation of p27 requires ubiquitination by the S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of ...
With regards to cell cycle related proteins silencing of PRPS2 significantly increased cyclin-dependent kinase inhibitor P27, ... PRPS2 knockdown significantly upregulated cyclin-dependent kinase inhibitor p27 but downregulated G1/S-specific protein cyclin ... by activating PARP/Bcl2/Caspase pathways and induced cell cycle G1 arrest at least partly attributed to cyclin-dependent kinase ... D) Western blot showed the protein levels of cell apoptosis-related proteins (cleavage of caspase-3, caspase-9, PARP, Bcl-2, ...
Upstream regulatory proteins, including cyclin-dependent kinase inhibitor 1A (CDKN1A) and MYC proto-oncogene, bHLH ... In this study, we screened for c-Myc inhibitors using a cell-dependent assay system in which the expression of c-Myc and its ... We used the Ascend to analyze 8881 proteins in HCT116 cancer cells treated with covalent sulfolane/sulfolene inhibitors of ... the Ascend was able to quantify hundreds more proteins than the Eclipse, many of them low-abundant proteins, and the Ascend was ...
The cyclin-dependent kinase inhibitor 2A protein, also known as p16,is a tumor suppressor protein encoded by the CDKN2A gene. ... The cyclin-dependent kinase inhibitor 2A protein, also known as p16,is a tumor suppressor protein encoded by the CDKN2A gene. ...
Cyclin-dependent kinase 4/6 inhibitors, known commonly as CDK 4/6 inhibitors, target two specific kinases, or proteins, called ... but CDK 4/6 inhibitors stop those signals and slow the growth of cancer. There are three CDK 4/6 inhibitors approved in the ... A new CDK 4/6 inhibitor was presented on June 5 as part of the ASCO Annual Meeting and is likely to add a fourth option in this ... Dalpiciclib is CDK 4/6 inhibitor that has shown signs of action against cancer in early studies and has proven to be safe, ...
Preliminary data had shown that inhibiting proteins called cyclin dependent kinases, or CDKs, might be effective against triple ... CDK inhibitors can block the impact of cyclin E/CDK action, helping to restore the beneficial effects of the TGF-beta/SMAD3 ... She found that these drugs could help to block the harmful impact of overexpression of cancer promoting cyclin E/CDKs, proteins ... researchers combined a new protein inhibitor with a chemotherapy drug to create a powerful combination that resulted in cancer ...
... which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. The protein is involved in ... It acts as a tumor suppressor and when the protein is lost, cells can undergo unscheduled replication, which may eventually ... Proton pump inhibitors for symptomatic control of symptomatic peptic ulcer disease due to hypergastrinemia ...
Furthermore, the proteins Pho81p, a cyclin-dependent kinase inhibitor, and Pcl7p, another Pho85p cyclin, were shown to be ... Thus, the stability of proteins involved in these cellular processes such as transcription factors, cyclin-dependent kinases, ... cyclin-dependent kinase Pho85p in complex with the cyclin Pcl5p. As initial step of Gcn4p stabilization upon amino acid ... This suggests a linkage between transcriptional activation and protein degradation. Keywords: Gcn4p; cyclins; transcription ...
... proteins of BCL-2 family, cyclins and cyclin dependent kinase inhibitors, protein-kinases and phosphatases, COX-2. 5-LOX, VEGF ... proteins of BCL-2 family, cyclins and cyclin dependent kinase inhibitors, protein-kinases and phosphatases, COX-2. 5-LOX, VEGF ...
... which is thought to support gene activation by the essential virus protein EBNA2. We have made an EBV in which the EBNA-LP gene ... We have investigated the role of an EBV protein (EBNA-LP) ... p53 and the cyclin-dependent kinase inhibitor p14ARF [55], ... Characterization of phenotypically distinct B-cell subsets and receptor-stimulated mitogen-activated protein kinase activation ... The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced ...
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993, 75 (4): 805-816. 10.1016 ... Cell cycle arrest in the S phase suggests that the kinase activity of CDK2-cyclin E, CDK2-cyclin A, and CDK1-cyclin A complexes ... P21 can suppress the kinase activities of CDK2-cyclin A and CDK1-cyclin A complexes, which are involved in the cell cycle ... CDK2-cyclin A, CDK1-cyclin A, and CDK1-cyclin B1 could eventually lead to the accumulation of cells in G2/M phase. Thus far, we ...
This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 ... a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA ... This summary is for the human ortholog.] The protein encoded by this gene contains a C-terminal RING finger domain, ...
Cyclin-Dependent Kinase Inhibitor Proteins [D12.776.167.187] Cyclin-Dependent Kinase Inhibitor Proteins ... This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, ... This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, ... Cell Cycle Proteins Entry term(s). Cell Cycle Regulatory Proteins Cell Division Cycle Proteins Cell-Cycle Regulatory Proteins ...
This result was supported by a high protein expression of the cyclin-dependent kinase inhibitor p16 in 44% of the tumours with ... G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and ... The pRb pocket, comprising the A and B cyclin-like domains, is the major focus of tumourigenic mutations in the protein. The ... In this study the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum has been ...
Protein (1 molecule). A. 1. Cyclin-dependent Kinase 4 Inhibitor a (P16ink4a) ...
  • Targeted overexpression of cyclin D1 to the mammary gland is sufficient for tumorigenesis, and cyclin D1 -/- mice are resistant to Ras-induced mammary tumors. (manipal.edu)
  • Overexpression of Cks1 has been reported in cancers of the breast colon lung belly bladder kidney mouth esophagus and ovary and this phenotype is often associated with down-regulation of SCFSkp2 target protein p27 and improved tumor aggressiveness (15-25). (biotech-angels.com)
  • Overexpression of Cks2 has been observed in cancers of the breast colon bladder esophagus belly mind and bile duct and PRT 062070 is often associated with an increased risk of metastasis and tumor recurrence (15 28 Previously we showed that overexpression of Cks proteins abrogates the intra-S phase checkpoint induced by replication stress potentially alleviating a critical barrier of oncoprotein-mediated transformation (38). (biotech-angels.com)
  • Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer. (unina.it)
  • In most cases, the observed overexpression of Skp2 protein was paralleled by an increase in the levels of Skp2 mRNA, and we observed Skp2 gene amplification at 5p13 in 2 out of 6 cell lines and in 9 out of 23 primary tumours (six out of eight ATCs, two out of nine PTCs and one out of six FTCs) using Q-PCR and/or fluorescence in situ hybridization analysis. (unina.it)
  • A growing number of evidence highlights that exceptional overexpression of apoptosis resistant proteins, and dysregulation of proliferation-related genes is obsessed in the advance of PCa [ 3 , 4 ]. (jcancer.org)
  • She found that these drugs could help to block the harmful impact of overexpression of cancer promoting cyclin E/CDKs, proteins that were inhibiting the tumor suppressant action of the TGF-beta/SMAD3 pathway. (scienceblog.com)
  • The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
  • Transcriptional repression of the cyclin D1 gene through distinct DNA sequences may contribute to the tumor suppressor function of the Ink4a/Arf locus. (manipal.edu)
  • CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. (wikipedia.org)
  • The gene codes for two proteins, including the INK4 family member p16 (or p16INK4a) and p14arf. (wikipedia.org)
  • This gene encodes two proteins, p16 and p14ARF, which are transcribed from the same second and third exons but alternative first exons: p16 from exon 1α and ARF from exon 1β. (wikipedia.org)
  • IGF2 , or insulin-like growth factor 2, is a paternally expressed protein-coding gene. (medscape.com)
  • CDKN1C , or cyclin-dependent kinase inhibitor 1C, is a gene that encodes a protein implicated in cell cycle regulation. (medscape.com)
  • KCNQ1OT1 , or potassium voltage-gated channel subfamily Q member 1 opposite transcript 1 is the antisense transcript of the protein-coding gene KCNQ1 . (medscape.com)
  • The second major emphasis of his laboratory relates to the functional properties of the precursor protein for IL-16, Pro-IL-16 as a tumor suppressor gene. (bu.edu)
  • The cyclin-dependent kinase inhibitor 2A protein, also known as p16,is a tumor suppressor protein encoded by the CDKN2A gene. (unipi.it)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (msdmanuals.com)
  • Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. (plos.org)
  • We have investigated the role of an EBV protein (EBNA-LP) which is thought to support gene activation by the essential virus protein EBNA2. (plos.org)
  • The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. (utsouthwestern.edu)
  • The CDKN1B gene provides instructions for making a protein called p27. (medlineplus.gov)
  • Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. (medlineplus.gov)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)
  • Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity. (cdc.gov)
  • In the case of some familial melanomas, researchers have discovered DNA changes in tumor suppressor genes, including CDKN2A (cyclin-dependent kinase inhibitor 2A) and BAP1 (BRCA1 associated protein-1). (skincancer.org)
  • abstract = "The Ink4a/Arf locus encodes two structurally unrelated tumor suppressor proteins, p16INK4a and p14ARF (murine p19ARF). (manipal.edu)
  • Invariant inactivation of either the p16INK4a-cyclin D/CDK-pRb pathway and/or p53-p14ARF pathway occurs in most human tumors. (manipal.edu)
  • The p16 (p16INK4A) protein is a cyclin-dependent kinase (CDK) inhibitor that plays an important regulatory role in the cell cycle. (clinisciences.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • It binds to CDK4/6 inhibiting its kinase activity and prevents Rb phosphorylation. (wikipedia.org)
  • Upon detection of DNA damage, the ATM kinase mediates the phosphorylation of the Mdm2 protein to block its interaction with p53. (reactome.org)
  • Also, phosphorylation of p53 at multiple loci, by the ATM kinase and by other kinases activated by the ATM kinase, stabilizes and activates the p53 protein. (reactome.org)
  • In sated cells, Gcn4p is weakly expressed and highly unstable, whereas its translation rate and protein stability increase upon amino acid limitation conditions.The amino acid-dependent Gcn4p degradation pathway is regulated via the phosphorylation by the nuclear cyclin-dependent kinase Pho85p in complex with the cyclin Pcl5p. (uni-goettingen.de)
  • G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. (diff.org)
  • An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN REPEATS. (uams.edu)
  • Invariant inactivation of either the p16 INK4a -cyclin D/CDK-pRb pathway and/or p53-p14 ARF pathway occurs in most human tumors. (manipal.edu)
  • Cyclin D1 is frequently overexpressed in breast cancer cells contributing an alternate mechanism inactivating the p16 INK4a /pRb pathway. (manipal.edu)
  • P16/Rb pathway collaborates with the mitogenic signaling cascade for the induction of reactive oxygen species, which activates the protein kinase C delta, leading to an irreversible cell cycle arrest. (wikipedia.org)
  • Skp2 is an essential member of the ubiquitin ligase protein degradation pathway responsive for degrading the cell cycle cyclin dependent kinase inhibitor p27. (bu.edu)
  • CDK inhibitors can block the impact of cyclin E/CDK action, helping to restore the beneficial effects of the TGF-beta/SMAD3 pathway, and thus facilitating cancer cell death. (scienceblog.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • It inhibits the cell cycle by acting as a scaffolding protein that assembles a histone deacetylase complex targeted via binding to GA-BP to the Skp2 promoter using intermolecular PDZ binding motifs. (bu.edu)
  • Degradation of p27 requires ubiquitination by the S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of Skp1-Cullin-F-box protein ubiquitin ligases. (unina.it)
  • Cks1 offers been shown to perform a specialized Cdk-independent function as a cofactor of the SCFSkp2 ubiquitin ligase PRT 062070 PRT 062070 which mediates the ubiquitin-dependent proteolysis PRT 062070 of Cdk inhibitors p27 p21 and Rb family protein p130 among others (11-13). (biotech-angels.com)
  • It is the physiological inhibitor of MDM2, an E3 ubiquitin ligase controlling the activity and stability of P53, and loss of P14ARF activity may have a similar effect as loss of P53. (wikipedia.org)
  • The MDM2 protein, usually interacts with p53 (Haupt et al, 1997 and Kubbutat et al, 1997), and by virtue of its E3 ubiquitin ligase activity, shuttles p53 to the cytoplasm and mediates its degradation by the ubiquitin-proteasome machinery. (reactome.org)
  • This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. (utsouthwestern.edu)
  • Whereas Pho81p interacts with Pcl5p only when Gcn4p is degraded, binding to Pcl7p is a constitutive process.The Pho85p substrate specificity for Gcn4p is mediated by the unstable cyclin Pcl5p. (uni-goettingen.de)
  • The control of Pcl5p sub-cellular localization was analyzed as a possible mechanism required for functional specificity of the kinase/cyclin complex. (uni-goettingen.de)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.com)
  • p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. (wikipedia.org)
  • The retinoblastoma tumor suppressor protein (pRb) regulates the cell cycle, facilitates differentiation, and restrains apoptosis. (diff.org)
  • Based on this function, p27 is described as a tumor suppressor protein. (medlineplus.gov)
  • Some mutations impair the protein's ability to interact with regulatory proteins, while others lead to the production of an unstable version of p27 that is quickly broken down. (medlineplus.gov)
  • This essential redundant function in mammalian development has been linked to impaired transcription of genes that encode mitotic regulators cyclin A cyclin B1 and Cdk1 resulting in cell cycle arrest in G2 phase. (biotech-angels.com)
  • To identify genes responsible for this progression, we carried out a genetic screening by an enhanced retroviral mutagen (ERM)-mediated random mutagenesis in the estrogen-dependent T47D breast cancer cells. (nih.gov)
  • The expression of a wide array of genes involved in the regulation of cell proliferation, apoptosis, neo-angiogenesis and invasion of tumors have been shown to be modulated by n-3 PUFAs (proteins of BCL-2 family, cyclins and cyclin dependent kinase inhibitors, protein-kinases and phosphatases, COX-2. (unicatt.it)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. (bvsalud.org)
  • The genetic changes and mechanisms underlying the progression of estrogen-dependent breast cancers to estrogen-independent, antiestrogen-resistant, and metastatic breast cancers are unclear despite being a major problem in endocrine therapy. (nih.gov)
  • Dalpiciclib is CDK 4/6 inhibitor that has shown signs of action against cancer in early studies and has proven to be safe, according to presenter Binghe Xu, MD . It is given as a daily pill for 3 weeks with a 1-week break until progression . (lbbc.org)
  • Selective rapid protein degradation is an important mechanism for distinct biological events, including cell cycle progression, signal-transduction, and differentiation. (uni-goettingen.de)
  • For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. (medlineplus.gov)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • The p53 protein activates the transcription of cyclin-dependent kinase inhibitor, p21. (reactome.org)
  • Recent studies suggest cyclin D1 and p16 INK4a expression are reciprocal in human breast cancers. (manipal.edu)
  • We have previously shown that Notch1 may function as a tumor suppressor and that histone deacetylase (HDAC) inhibitors can induce Notch1 expression in some endocrine cancers. (aacrjournals.org)
  • By controlling the transition between the G1 and S phases through regulation of retinoblastoma protein, p16 decelerates cellular differentiation and therefore acts as a tumor suppressor, making it the key marker in several human cancers including head and neck cancer, perianal lesions, melanomas, gliomas, lymphomas, and some types of leukemia. (clinisciences.com)
  • Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. (medscimonit.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • Here we investigated the expression of PRPS2 protein in human PCa and paired normal tissues by immunohistochemistry, meanwhile the regulatory effects on cell proliferation, apoptosis and growth of xenograft tumors in nude mice were evaluated in PCa cells with PRPS2 depletion. (jcancer.org)
  • The retinoblastoma protein (abbreviated pRb or Rb ) is a tumor suppression protein of 110 kDa that is dysfunctional in many types of cancer. (diff.org)
  • The Ink4a/Arf locus encodes two structurally unrelated tumor suppressor proteins, p16 INK4a and p14 ARF (murine p19 ARF ). (manipal.edu)
  • This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)
  • Cks1 and Cks2 are adaptor-like proteins that bind many cyclin-dependent kinases (Cdks). (biotech-angels.com)
  • Preliminary data had shown that inhibiting proteins called cyclin dependent kinases, or CDKs, might be effective against triple negative breast cancer. (scienceblog.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • We found that T47D cells contain only one p27kip1 (p27) allele coding for the p27 cyclin-dependent kinase (CDK) inhibitor. (nih.gov)
  • Repression of cyclin D1 by p16 INK4a occurred independently of the p16 INK4a -cdk4-binding function and required a cAMP-response element/activating transcription factor-2-binding site. (manipal.edu)
  • A wealth of clinical studies has shown that Cks proteins likely play important causative tasks in human being tumorigenesis. (biotech-angels.com)
  • P14ARF induces cell cycle arrest in G2 phase and subsequent apoptosis in a P53-dependent and P53-independent manner, and thus is regarded as a tumor suppressor. (wikipedia.org)
  • Here, we showed that although there was minimal Notch1 expression in follicular thyroid cancer FTC236 and papillary thyroid cancer DRO cells, transfection of constitutive Notch1 plasmid into these cells led to growth inhibition, down-regulation of cyclin D1, and up-regulation of p21. (aacrjournals.org)
  • These results indicate that HDAC inhibitors activate Notch1 signaling in thyroid cancer cells and lead to the suppression of proliferation by cell cycle arrest. (aacrjournals.org)
  • To analyse the importance of Gcn4p turnover for the transcriptional activity of this protein, a stabilized Gcn4p version was created by the expression of GCN4LEU267SER or deletion of PCL5. (uni-goettingen.de)
  • This suggests a linkage between transcriptional activation and protein degradation. (uni-goettingen.de)
  • The protein is involved in cellular growth and development and has an important role in regulating the cell cycle. (msdmanuals.com)
  • Thus, the stability of proteins involved in these cellular processes such as transcription factors, cyclin-dependent kinases, and cyclins depend on different environmental changes. (uni-goettingen.de)
  • Some viral oncoproteines, but also many cellular proteins that interact with pRb, contain a preserved motive LxCxE with which they tie the pocket domain. (diff.org)
  • Cyclin-Dependent Kinase Inhibitor p19" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uams.edu)
  • Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (medlineplus.gov)
  • The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. (plos.org)
  • Treatment of FTC236 cells with HDAC inhibitors valproic acid (1-4 mmol/L) or suberoyl bishydroxamic acid (10-30 μmol/L) induced functional Notch1 protein expression and suppressed cell growth in a dose-dependent manner. (aacrjournals.org)
  • Herein, reciprocal regulation of cyclin D1 and p16 INK4a was observed in tissues of mice mutant for the Ink4a/Arf locus. (manipal.edu)
  • This protein is found in cells and tissues throughout the body. (medlineplus.gov)
  • studies suggest that certain endocrine cells may be particularly dependent on the p27 protein to control cell division. (medlineplus.gov)
  • This protein belongs to the CDKN2 cyclin-dependent kinase inhibitor family. (wikipedia.org)
  • Demographic and that this particular family of angiogenic clinical data were collected during routine proteins plays an important role in placental obstetric visits. (who.int)
  • The pRb pocket, comprising the A and B cyclin-like domains, is the major focus of tumourigenic mutations in the protein. (diff.org)
  • It acts as a tumor suppressor and when the protein is lost, cells can undergo unscheduled replication, which may eventually lead to cancer. (msdmanuals.com)
  • p16 INK4a repressed cyclin D1 expression and transcription. (manipal.edu)
  • Aberrant expression of this protein has been associated with TESTICULAR CANCER. (uams.edu)
  • Loss of expression of the cyclin-dependent kinase inhibitor p27 through enhanced protein degradation frequently occurs in human cancer. (unina.it)
  • Phosphoribosyl pyrophosphate synthetases 2 (PRPS2) protein function as nucleotide synthesis enzyme that plays vital roles in cancer biology. (jcancer.org)
  • The amount of Gcn4p is mainly regulated via control of its protein synthesis in the cytoplasm and control of protein degradation in the nucleus. (uni-goettingen.de)
  • Both proteins are nuclear and constantly present and not required for dissociation of Pho85p/Pcl5p in response to amino acid starvation conditions. (uni-goettingen.de)
  • In contrast, the β-importin Kap95p has been identified to be required for nuclear import of this cyclin. (uni-goettingen.de)
  • Furthermore, the proteins Pho81p, a cyclin-dependent kinase inhibitor, and Pcl7p, another Pho85p cyclin, were shown to be required for amino acid-dependent Gcn4p stabilization. (uni-goettingen.de)
  • Western blot analysis revealed the reduction of cyclin D1 and the increase of p21 in HDAC inhibitor-treated cells. (aacrjournals.org)
  • and third, growth factor receptor binding protein 2-associated binder 2 (Gab2) and Akt activity were increased following E2F1 overactivation, leading to a significant enhancement of cell migration and invasion. (nih.gov)