Cyclin-dependent Kinase Inhibitor Protein
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Cyclin-dependent Kinase Inhibitor Protein
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 restriction point, arrest at the G1 phase, 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

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Cyclin-dependent Kinase
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The c ...
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CDKN2D
Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the ''CDKN2D'' gene. The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. The expression of this gene and its protein product (p19) is observed in neurons with neurofibrillary tangles (NFTs) and it is suggested as a marker for senescent neurons. Two alternatively spliced variants of this gene, which encode an identical pr ...
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CDKN1C
Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the ''CDKN1C'' imprinted gene. Function Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations of CDKN1C are implicated in sporadic cancers and Beckwith-Wiedemann syndrome suggesting that it is a tumor suppressor candidate. CDKN1C is a tumor suppressor human gene on chromosome 11 (11p15) and belongs to the ''cip/kip'' gene family. It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes. Thus p57KIP2 causes arrest of the cell cycle in G1 phase. CDKN1C was found to lead to cancer cell dormancy; its gene expression is regulated through the activity of glucocorticoid receptors (GRs) through chromatin remodelling mediated by SWI/SNF. Clinical significance A mutation of this gene may lead to loss of control over the cell cycle leading to uncontr ...
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Cyclin-dependent Kinase Inhibitor 1C
Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the ''CDKN1C'' imprinted gene. Function Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations of CDKN1C are implicated in sporadic cancers and Beckwith-Wiedemann syndrome suggesting that it is a tumor suppressor candidate. CDKN1C is a tumor suppressor human gene on chromosome 11 (11p15) and belongs to the ''cip/kip'' gene family. It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes. Thus p57KIP2 causes arrest of the cell cycle in G1 phase. CDKN1C was found to lead to cancer cell dormancy; its gene expression is regulated through the activity of glucocorticoid receptors (GRs) through chromatin remodelling mediated by SWI/SNF. Clinical significance A mutation of this gene may lead to loss of control over the cell cycle leading to uncont ...
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Cyclin D3
G1/S-specific cyclin-D3 is a protein that in humans is encoded by the ''CCND3'' gene. Function The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Clinical significance Mutations in ''CCND3'' are implicated in cases of breast cancer. Interactions Cyclin ...
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CDKN1B
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 ...
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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 initi ...
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Cyclin E1
G1/S-specific cyclin-E1 is a protein that in humans is encoded by the ''CCNE1'' gene. Function The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which ...
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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-terminal dom ...
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CDKN2C
Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the ''CDKN2C'' gene. Function The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported. Interactions CDKN2C has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6 Cell division protein kinase 6 (CDK6) is an enzyme encoded by t ...
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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 subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei ( eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis). During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the mitotic phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps ...
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CDKN2B
Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is encoded by the ''CDKN2B'' gene in humans. Function This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated, deleted, or disregulated in a wide variety of cancer. This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases by cyclin D, thus the encoded protein functions as a cell growth regulator that inhibits cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcripts of this gene encode proteins that share the N-terminal sequence but completely differ in the C-terminus. Interactions CDKN2B tumor suppressor gene product p15 has been shown to interact w ...
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