Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21)
1_MSEPA 6_ GDVRQ 11_ NPCGS 16_ KACRR 21_ LFGPV 26_ DSEQL 31_ SRDCD 36_ ALMAG 41_ CIQEA 46_ RERWN 51_ FDFVT 56_ ETPLE 61_ GDFAW 66_ ERVRG 71_ LGLPK 76_ LYLPT 81_ GPRRG 86_ RDELG 91_ GGRRP 96_ GTSPA 101_ LLQGT 106_ AEEDH 111_ VDLSL 116_ SCTLV 121_ PRSGE 126_ QAEGS 131_ PGGPG 136_ DSQGR 141_ KRRQT 146_ SMTDF 151_ YHSKR 156_RLIFS
1: 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)