This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]
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Function:
Function:May be the important intermediate by which p53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression.,induction:By p53, mezerein (antileukemic compound) and interferon beta.,PTM:Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA.,similarity:Belongs to the CDI family.,tissue specificity:Expressed in all adult human tissues, with 5-fold lower levels observed in the brain.,
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Cellular Localization:
Cytoplasmic, Nuclear
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Tissue Expression:
Expressed in all adult tissues, with 5-fold lower levels observed in the brain.