Recombinant Mouse Cyclin-dependent kinase inhibitor 1 (Cdkn1a)

Function

Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:37178686). 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 (PubMed:37178686). 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 (PubMed:25329316). Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (By similarity). 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 (PubMed:36689330)

Subcellular Location

Cytoplasm; Nucleus

Tissue Specificity

Expressed in keratinocytes (at protein level)

Subunit

Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (PubMed:20154723). Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. 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. 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. Interacts with PIM1 (By similarity). Interacts with STK11 (PubMed:25329316). Interacts with NUAK1 (By similarity). Interacts with DTL and TRIM39 (By similarity). Interacts with PKP3; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (PubMed:36689330)

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• Li Z. et al. An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis. — Oncogene (2010)
• Esteve-Puig R. et al. A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation. — PLoS Genet. (2014)
• Saito A. et al. p53-independent tumor suppression by cell-cycle arrest via CREB/ATF transcription factor OASIS. — Cell Rep. (2023)
• Mueller L. et al. Plakophilin 3 facilitates G1/S phase transition and enhances proliferation by capturing RB protein in the cytoplasm and promoting EGFR signaling. — Cell Rep. (2023)