CHEK1, EnkiLife, AMRe05875

Chk1 kinase acts downstream of ATM/ATR kinase and plays an important role in DNA damage checkpoint control, embryonic development, and tumor suppression. Activation of Chk1 involves phosphorylation at Ser317 and Ser345 by ATM/ATR, followed by autophosphorylation of Ser296. Activation occurs in response to blocked DNA replication and certain forms of genotoxic stress. Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed: 11535615, PubMed: 12446774, PubMed: 12399544, PubMed: 14559997, PubMed: 14988723, PubMed: 15311285, PubMed: 15665856, PubMed: 15650047, PubMed: 32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed: 11535615, PubMed: 12446774, PubMed: 12399544, PubMed: 14559997, PubMed: 14988723, PubMed: 15311285, PubMed: 15665856, PubMed: 15650047). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed: 11535615, PubMed: 12446774, PubMed: 12399544, PubMed: 14559997, PubMed: 14988723, PubMed: 15311285, PubMed: 15665856, PubMed: 15650047). Recognizes the substrate consensus sequence [R-X-X- S/T] (PubMed: 11535615, PubMed: 12446774, PubMed: 12399544, PubMed: 14559997, PubMed: 14988723, PubMed: 15311285, PubMed: 15665856, PubMed: 15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed: 9278511, PubMed: 12676583, PubMed: 14681206, PubMed: 12676925, PubMed: 12759351, PubMed: 19734889, PubMed: 14559997). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed: 9278511). Phosphorylation of CDC25A at 'Ser- 76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed: 9278511, PubMed: 12676583, PubMed: 14681206, PubMed: 12676925, PubMed: 12759351, PubMed: 19734889). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed: 9278511, PubMed: 19734889, PubMed: 20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed: 9278511). Also phosphorylates NEK6 (PubMed: 18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed: 15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed: 10673501, PubMed: 15659650, PubMed: 16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed: 17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed: 12660173, PubMed: 12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed: 12660173, PubMed: 12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed: 18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3. 1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed: 17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed: 31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed: 33108758).