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PubMed · 15736430

Chkl binds and phosphorylates BAD protein.

Edward Kyu-ho Han·Chris Butler·Haichao Zhang·Jean M Severin·Wenying Qin·Tom F Holzman·Earl J Gubbins·Robert L Simmer·Saul Rosenberg·Vincent L Giranda·Shi-Chung Ng·Y Luo
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Abstract

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.

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Amino Acid SequenceCarrier ProteinsCell LineCheckpoint Kinase 1Embryo, MammalianHumansKidneyMolecular Sequence DataPolyisoprenyl PhosphatesProtein BindingProtein Kinasesbcl-Associated Death ProteinJournal Article

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Edward Kyu-ho Han, Chris Butler, Haichao Zhang, Jean M Severin, Wenying Qin, Tom F Holzman, Earl J Gubbins, Robert L Simmer, Saul Rosenberg, Vincent L Giranda, Shi-Chung Ng, Y Luo. Chkl binds and phosphorylates BAD protein.. https://pubmed.ncbi.nlm.nih.gov/15736430/

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