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P21
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-term ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromosome 6
Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA in cells. It contains the major histocompatibility complex, which contains over 100 genes related to the immune response, and plays a vital role in organ transplantation. Genes The human leukocyte antigen lies on chromosome 6, with the exception of the gene for β2-microglobulin (which is located on chromosome 15), and encodes cell-surface antigen-presenting proteins among other functions. Number of genes In 2003, the entirety of chromosome 6 was manually annotated for proteins, resulting in the identification of 1,557 genes, and 633 pseudogenes. The following are some of the newer gene count estimates. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome v ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, ... [...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 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-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 interacts with the RBX1/ ... [...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 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 protei ... [...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 Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of '' S. cerevisiae'' cdc28, and '' 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 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 also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription ... [...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 contain ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclin-dependent Kinase 2
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 Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of '' S. cerevisiae'' cdc28, and '' 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 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 also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Cycle Checkpoint
Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein. Background All living organisms are the products of repeated rounds of cell growth and divisio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA ( DNA replication) and some of its organelles, and sub ... progression is delayed or stopped by cyclin-dependent kinase inhibitors, abbreviated CDIs, CKIs or CDKIs. CDIs are involved in cell cycle arrest 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 disso ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclin-dependent Kinase 6
Cell division protein kinase 6 (CDK6) is an enzyme encoded by the ''CDK6'' gene. It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. CDK family members are highly similar to the gene products of ''Saccharomyces cerevisiae'' cdc28, and ''Schizosaccharomyces pombe'' cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point. This kinase is a catalytic subunit of the protein kinase complex, important for the G1 phase progression and G1/S transition of the cell cycle and the complex is composed also by an activating sub-unit; the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
