Scientific background: |
CHK2, a protein kinase that is activated in response to DNA damage, is involved in cell cycle arrest. Mapped on 22q12.1, CHK2 has a potential regulatory region rich in SQ and TQ amino acid pairs. It regulates BRCA1 function after DNA damage by phosphorylating serine-988 of BRCA1. Additionally, CHK2 can be modified by phosphorylation and activated in response to ionizing radiation, and can be also modified in response to hydroxyurea treatment. Furthermore, oligomerization of CHEK2 increases the efficiency of transautophosphorylation, resulting in the release of active CHEK2 monomers that proceed to enforce checkpoint control in irradiated cells. Morever, CHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and that their observations provided a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast. There is a wide expression of small amounts of CHK2 mRNA with larger amounts in human testis, spleen, colon, and peripheral blood leukocytes. |
References: |
1. Lee, J.-S.; Collins, K. M.; Brown, A. L.; Lee, C.-H.; Chung, J. H. : hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404: 201-204, 2000.
2. Brown, A. L.; Lee, C.-H.; Schwarz, J. K.; Mitiku, N.; Piwnica-Worms, H.; Chung, J. H. : A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Proc. Nat. Acad. Sci. 96: 3745-3750, 1999.
3. Ahn, J.-Y.; Li, X.; Davis, H. L.; Canman, C. E. : Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J. Biol. Chem. 277: 19389-19395, 2002.
4. Bell, D. W.; Varley, J. M.; Szydlo, T. E.; Kang, D. H.; Wahrer, D. C. R.; Shannon, K. E.; Lubratovich, M.; Verselis, S. J.; Isselbacher, K. J.; Fraumeni, J. F.; Birch, J. M.; Li, F. P.; Garber, J. E.; Haber, D. A. : Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286: 2528-2531, 1999. |