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CDKN1A
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-termina ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclin-dependent Kinase Inhibitor
A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein that inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. CKIs are vital proteins within the control system that point out whether the processes of DNA synthesis, mitosis, and cytokines control one another. When a malfunction hinders the successful completion of DNA synthesis in the G1 phase, it triggers a signal that delays or halts the progression to the S phase. Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer. CKI Inactivation Process Cyclin-dependent kinase inhibitor proteins work by inactivating the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CDK2
Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ''CDK2'' gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of serine/threonine-specific protein kinase, Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of ''Saccharomyces cerevisiae, S. cerevisiae'' cdc28, and ''Schizosaccharomyces pombe, S. pombe'' cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or cyclin A, A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is als ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 contai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase delta, DNA polymerase δ in eukaryotic cell (biology), 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
World Health Organization
The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Geneva, Switzerland, and has 6 regional offices and 150 field offices worldwide. Only sovereign states are eligible to join, and it is the largest intergovernmental health organization at the international level. The WHO's purpose is to achieve the highest possible level of health for all the world's people, defining health as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." The main functions of the World Health Organization include promoting the control of epidemic and endemic diseases; providing and improving the teaching and training in public health, the medical treatment of disease, and related matters; and promoting the establishment of international standards for biologic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TNM Staging System
The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the anatomical extent of the spread of malignant tumours (cancer). It has gained wide international acceptance for many solid tumor cancers, but is not applicable to leukaemia or tumors of the central nervous system. Most common tumors have their own TNM classification. The TNM staging system is sometimes referred to as the AJCC/UICC staging system or the UICC/AJCC staging system. Several revisions have been published, the latest being the eighth edition in 2017. 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 alph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL4A
Cullin-4A is a protein that in humans is encoded by the ''CUL4A'' gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the Cell cycle, mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide. Structure CUL4A protein is 759 amino acids long and forms an extended, rigid structure primarily consisting of alpha helix, alpha-helices. At the N-terminus, CUL4A binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). As a result, the N-terminus is crucial for the recruitment of substrates for the ubiquitin ligase complex. At the C-terminal end, CUL4A inte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 re ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitin Ligases
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclin E
Cyclin E is a member of the cyclin family. Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27Kip1 (an inhibitor of Cyclin D), tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase. Functions of Cyclin E Like all cyclin family members, cyclin E forms complexes with cyclin-dependent kinases. In particular, Cyclin E binds with CDK2. Cyclin E/CDK2 regulates multiple cellular processes by phosphorylating numerous downstream proteins. Cyclin E/CDK2 plays a critical role in the G1 phase and in the G1-S phase transition In physics, chemistry, and other related fields like biology, a phase transition (or phase change) is the physical process of transition between one state of a medium and another. Commonly the term is used to refer to changes among the basic Sta .... Cyclin E/CDK2 phosphor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
