TY - JOUR T1 - Chk1 Binds and Phosphorylates BAD Protein JF - Anticancer Research JO - Anticancer Res SP - 3907 LP - 3910 VL - 24 IS - 6 AU - EDWARD KYU-HO HAN AU - CHRIS BUTLER AU - HAICHAO ZHANG AU - JEAN M. SEVERIN AU - WENYING QIN AU - TOM F. HOLZMAN AU - EARL J. GUBBINS AU - ROBERT L. SIMMER AU - SAUL ROSENBERG AU - VINCENT L. GIRANDA AU - SHI-CHUNG NG AU - Y. LUO Y1 - 2004/11/01 UR - http://ar.iiarjournals.org/content/24/6/3907.abstract N2 - Chk1 (checkpoint kinase 1) is a serine-threonine kinase that is critical for G2/M arrest in response to DNA damage. Chk1 phosphorylates Cdc25C at serine-216, a major regulatory site, in response to DNA damage. Furthermore, Chk1 also phosphorylates Cdc25A on serine 123 which accelerates its degradation through the ubiquitin-proteasome pathway and arrests cells in late G2-phase after DNA damage. In the present study, we demonstrated that Chk1 phosphorylates pro-apoptotic protein BAD (Bcl-2/Bcl-XL-Antagonist, causing cell Death) in vitro. In vitro phosphorylation analysis with various mouse BAD peptides has revealed two phosphorylation sites for Chk1 at serine-155 and serine-170. When wild-type and mutant BAD (S155A) constructs were transfected into 293T cells, an association between BAD and Chk1 was observed by co-immunoprecipitation. In addition, there was an increase in the phosphorylation of serine-155 following DNA damage by adriamycin treatment. Our results suggest that Chk1 associates with BAD and phosphorylates the BAD protein at serine-155. Taken together, our results suggest that Chk1 may inactivate BAD by associating with and phosphorylating residues critical for BAD function in response to DNA damage. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -