Chkl binds and phosphorylates BAD protein

Anticancer Res. 2004 Nov-Dec;24(6):3907-10.

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.

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / metabolism*
  • Cell Line
  • Checkpoint Kinase 1
  • Embryo, Mammalian
  • Humans
  • Kidney / cytology
  • Molecular Sequence Data
  • Polyisoprenyl Phosphates
  • Protein Binding
  • Protein Kinases / metabolism*
  • bcl-Associated Death Protein

Substances

  • BAD protein, human
  • Carrier Proteins
  • Polyisoprenyl Phosphates
  • bcl-Associated Death Protein
  • phosprenyl
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Chek1 protein, mouse