| Description | 61 kDa. Isoform a: 543 amino acids; isoform b: 514 amino acids. Contains FHA and ser/thr kinase domains. Molecular studies of Chk2 typically do not distinguish between the different isoforms. |
| Expression | All tissues tested. |
| Localisation | nuclear |
| Function | Chk2 plays a role in the DNA damage signal cascade, especially in response to double-strand breaks. After detection of DNA damage, Chk2 is phosphorylated on Thr-68 by ATM and ATR. Thus activated, Chk2 targets p53 for phosphorylation on Ser20, releasing p53 from its inhibitor MDM2 and allowing transcriptional activation of genes responsible for cell cycle arrest, such as p21waf1/cip1, as well as initiation of apoptosis. In S phase, Chk2 phosphorylates Cdc25A on Ser123, targeting it for degradation and making it unavailable for the activation of cdk2, thus inhibiting the advance of S phase. In G2 phase, Chk2 phosphorylates Ser216 of Cdc25C, blocking entry into mitosis. Chk2 is also involved in the regulation of BRCA1. Under normal conditions the two proteins are associated; after irradiation Chk2 phosphorylates Ser988 of BRCA1. This step is required for their dissociation, and the liberated BRCA1 participates directly in DNA repair and cell cycle arrest. Finally, Chk2 can provoke apoptosis independently of p53, for example via phosphorylation of PML. |
| Homology | 26 % identical to the Rad53 S. cereviscea homolog. The FHA and kinase domains are particularly conserved. |
| Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. |
| Matsuoka S, Huang M, Elledge SJ |
| Science (New York, N.Y.). 1998 ; 282 (5395) : 1893-1897. |
| PMID 9836640 |
| |
| DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. |
| Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY |
| Oncogene. 1999 ; 18 (55) : 7883-7899. |
| PMID 10630641 |
| |
| p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. |
| Vahteristo P, Tamminen A, Karvinen P, Eerola H, Eklund C, Aaltonen LA, Blomqvist C, Aittomˆ§ki K, Nevanlinna H |
| Cancer research. 2001 ; 61 (15) : 5718-5722. |
| PMID 11479205 |
| |
| Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. |
| Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP |
| Genes, chromosomes & cancer. 2002 ; 33 (1) : 17-21. |
| PMID 11746983 |
| |
| Contribution of the CHEK2 1100delC variant to risk of multiple colorectal adenoma and carcinoma. |
| Lipton L, Fleischmann C, Sieber OM, Thomas HJ, Hodgson SV, Tomlinson IP, Houlston RS |
| Cancer letters. 2003 ; 200 (2) : 149-152. |
| PMID 14568168 |
| |
| Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. |
| Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton MR, Breast Cancer Linkage Consortium, Rahman N |
| American journal of human genetics. 2003 ; 72 (4) : 1023-1028. |
| PMID 12610780 |
| |
| CHEK2 1100delC is not a risk factor for male breast cancer population. |
| Syrjˆ§koski K, Kuukasjˆ§rvi T, Auvinen A, Kallioniemi OP |
| International journal of cancer. Journal international du cancer. 2004 ; 108 (3) : 475-476. |
| PMID 14648717 |
| |