Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
The Cockayne Syndrome group B (CSB) protein plays important roles in transcription, transcription-coupled nucleotide excision repair and base excision DNA repair. c-Abl kinase also plays a role in DNA repair as a regulator/coordinator of the DNA damage response. This study presents evidence that the N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. The subcellular localization of CSB to the nucleus and nucleolus is altered after phosphorylation by c-Abl. c-Abl-dependent phosphorylation of CSB increased in cells treated with hydrogen peroxide and decreased in cells pre-treated with STI-571, a c-Abl-specific protein kinase inhibitor. Activation of the c-Abl kinase in response to oxidative damage is not observed in CSB null cells. These results suggest that c-Abl and CSB may regulate each other in a reciprocal manner in response to oxidative stress.
Imam
Syed Z
SZ
Laboratory of Molecular Gerontology, National Institutes on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Indig
Fred E
FE
Cheng
Wen-Hsing
WH
Saxena
Satya P
SP
Stevnsner
Tinna
T
Kufe
Donald
D
Bohr
Vilhelm A
VA
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D016315:Proto-Oncogene Proteins c-abl / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000075223:Poly-ADP-Ribose Binding Proteins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes