Recombinant Human Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Function

Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity)

Subcellular Location

Cytoplasm; Nucleus

Tissue Specificity

Expressed in all adult tissues, with 5-fold lower levels observed in the brain

Subunit

Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (By similarity). Interacts with MKRN1 (PubMed:19536131). Interacts with PSMA3 (PubMed:11350925). Interacts with PCNA (PubMed:11595739, PubMed:18703516, PubMed:18794347, PubMed:8861913). Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4 (PubMed:9106657). Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair (PubMed:19445729). Interacts with PIM1 (PubMed:12431783). Interacts with STK11 and NUAK1 (PubMed:25329316). Interacts wih DTL (PubMed:23213251). Interacts with isoform 1 and isoform 2 of TRIM39 (PubMed:23213251). Interacts with PKP3; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (By similarity)

• Harper J.W. et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. — Cell (1993)
• El-Deiry W.S. et al. WAF1, a potential mediator of p53 tumor suppression. — Cell (1993)
• Xiong Y. et al. p21 is a universal inhibitor of cyclin kinases. — Nature (1993)
• Jiang H. et al. Use of a sensitive and efficient subtraction hybridization protocol for the identification of genes differentially regulated during the induction of differentiation in human melanoma cells. — Mol. Cell. Differ. (1993)
• Jiang H. et al. The melanoma differentiation-associated gene mda-6, which encodes the cyclin-dependent kinase inhibitor p21, is differentially expressed during growth, differentiation and progression in human melanoma cells. — Oncogene (1995)
• Noda A. et al. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. — Exp. Cell Res. (1994)
• Mousses S. et al. Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer. — Hum. Mol. Genet. (1995)
• PubMed: CI-6QALJ9DN355KS (APR-)