WAF1
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WAF1
p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2. p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest.Waldman, Todd, Kenneth W. Kinzler, and Bert Vogelstein. "p21 is necessary for the p53-mediated G1 arrest in human cancer cells." Cancer research 55.22 (1995): 5187-5190. This protein is encoded by the ''CDKN1A'' gene located on chromosome 6 (6p21.2) in humans. Function CDK inhibition p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4 /6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase. The binding of p21 to CDK complexes occurs through p21's N-terminal dom ...
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PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics. Many proteins interact with PCNA via the two known PCNA-interacting motifs PCNA-interacting peptide (PIP) box and AlkB homologue 2 PCNA interacting motif (APIM). Proteins binding to PCNA via the PIP-box are mainly involved in DNA replication whereas proteins binding to PCNA via APIM are mainly important in the context of genotoxic stress. Function The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ...
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TP53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence ''TP53'' ''italics'' are used to denote the ''TP53'' gene name and distinguish it from the protein it encodes is classified as a tumor suppressor gene. The name p53 was given in 1979 describing the apparent molecular mass; SDS-PAGE analysis indicates that it is a 53-kilodalton (kDa) protein. However, the actual mass of the full-length p53 protein (p53α) based on the sum of masses of the amino acid residues is only 43.7 kDa. This difference is due to the high number of proline residues in the protein, ...
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Cyclin-dependent Kinase 4
Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the ''CDK4'' gene. CDK4 is a member of the cyclin-dependent kinase family. Function The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of ''S. cerevisiae'' cdc28 and ''S. pombe'' cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb). Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociati ...
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P27 (gene)
Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes a protein which belongs to the ''Cip/Kip'' family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle. Function The p27Kip1 gene has a DNA sequence similar to other members of the "Cip/Kip" family which include the p21Cip1/Waf1 and p57Kip2 genes. In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules. For example, p27Kip1 binds to cyclin D either alone, or when complexed to its catalytic subunit CDK4. In doing so p27Kip1 inhibits the catalytic activ ...
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SKP2
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the ''SKP2'' gene. Structure and function Skp2 contains 424 residues in total with the ~40 amino acid F-box domain lying closer to the N-terminal region at the 94-140 position and the C-terminal region forming a concave surface consisting of ten leucine-rich repeats (LRRs). The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which often—but not always—recognize substrates in a phosphorylation-dependent manner. In this SCF complex, Skp2 acts as the substrate recognition factor. F-box Domain The F-box proteins are divided into three classes: Fbxws containing WD40 repeat domains, Fbxls containing leucine-rich repeats, and Fbxos containing either different protein–protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxls class. In addition to an F-box, this protein contains 10 ...
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Cyclin-dependent Kinase Inhibitor
A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). Several function as tumor suppressor proteins. Cell cycle progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. CDIs are involved in cell cycle arrest An arrest is the act of apprehending and taking a person into custody (legal protection or control), usually because the person has been suspected of or observed committing a crime. After being taken into custody, the person can be questi ... at the G1 phase. Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. They are named by the small letter "p" followed by their molecular weight in kilodaltons. They are p15, p16, p18, p19, p21, p27, and p57. Associated gene and target References External links * Protein domains {{protein-stub ...
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Cyclin
Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. Etymology Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins. In an interview for "The Life Scientific" (aired on 13/12/2011) hosted by Jim Al-Khalili, R. Timothy Hunt explained that the name "cyclin" was originally named after his hobby cycling. It was only after the naming did its importance in the cell cycle become apparent. As it was appropriate the name stuck. R. Timothy Hunt: "By the way, the name cyclin, which I coined, was really a joke, it's because I liked cycling so much at the time, but they did come and go in the cell..." Function Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. (Note that the cyclins are now classified according to their conse ...
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Overall Survival Rate
Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be used for the assessment of standards of therapy. The survival period is usually reckoned from date of diagnosis or start of treatment. Survival rates are based on the population as a whole and cannot be applied directly to an individual. There are various types of survival rates (discussed below). They often serve as endpoints of clinical trials and should not be confused with mortality rates, a population metric. Overall survival Patients with a certain disease (for example, colorectal cancer) can die directly from that disease or from an unrelated cause (for example, a car accident). When the precise cause of death is not specified, this is called the overall survival rate or observed survival rate. Doctors often use mean overall survival ...
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TNM Staging System
The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the extent of spread of cancer. It is a classification system of the anatomical extent of tumor cancers. It has gained wide international acceptance for many solid tumor cancers, but is not applicable to leukaemia and tumors of the central nervous system. Most common tumors have their own TNM classification. Sometimes also described as the AJCC system. TNM was developed and is maintained by the Union for International Cancer Control (UICC). It is also used by the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). In 1987, the UICC and AJCC staging systems were unified into the single TNM staging system. TNM is a notation system that describes the stage of a cancer, which originates from a solid tumor, using alphanumeric codes: *T describes the size of the original (primary) tumor and whether it has invaded nearby tissue, *N ...
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CASP3
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this g ...
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World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of health". Headquartered in Geneva, Switzerland, it has six regional offices and 150 field offices worldwide. The WHO was established on 7 April 1948. The first meeting of the World Health Assembly (WHA), the agency's governing body, took place on 24 July of that year. The WHO incorporated the assets, personnel, and duties of the League of Nations' Health Organization and the , including the International Classification of Diseases (ICD). Its work began in earnest in 1951 after a significant infusion of financial and technical resources. The WHO's mandate seeks and includes: working worldwide to promote health, keeping the world safe, and serve the vulnerable. It advocates that a billion more people should have: universal health care coverag ...
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SCF Complex
Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. The SCF complex also marks various other cellular proteins for destruction. Core components SCF contains a variable F-box protein and three core subunits: *F-box protein (FBP) – FBP contributes to the substrate specificity of the SCF complex by first aggregating to target proteins independently of the complex. Each FBP (e.g. Skp2) may recognize several different substrates in a manner that is dependent on post-translational modifications such as phosphorylation or glycosylation. FBP then binds to Skp1 of the SCF complex using an F-box motif, bringing the target protein into proximity with the functional E2 ubiquitin-conjugating enzyme. FBP is also essential in reg ...
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