Abstract
CHK1 regulates the DNA damage-induced checkpoint involving an ATR- or ATM- dependent pathway. In this paper, we focused on the autophosphorylation of Ser296, one of the DNA damage-induced phosphorylation sites. First, we demonstrated that the Ser296 autophosphorylation of CHK1 is mainly regulated by an intramolecular mechanism in response to DNA damage. In examining the relationship between Ser296 and Ser317/Ser345, the other ATR dependent phosphorylation sites, we found that the Ser296 cis-autophosphorylation was dependent on both Ser317 and Ser345 phosphorylation. Our findings suggest that CHK1 mediates cell cycle checkpoint signals by both cis-autophosphorylation and trans-phosphorylation of downstream factors.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Ataxia Telangiectasia Mutated Proteins
-
Blotting, Western
-
Cell Cycle Checkpoints
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism
-
Cell Line, Tumor
-
Checkpoint Kinase 1
-
DNA Damage*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
HeLa Cells
-
Humans
-
Mutagenesis, Site-Directed
-
Phosphorylation
-
Protein Kinases / genetics
-
Protein Kinases / metabolism*
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
RNA Interference
-
Serine / genetics
-
Serine / metabolism*
-
Signal Transduction*
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism
Substances
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
Tumor Suppressor Proteins
-
Serine
-
Protein Kinases
-
ATM protein, human
-
ATR protein, human
-
Ataxia Telangiectasia Mutated Proteins
-
CHEK1 protein, human
-
Checkpoint Kinase 1
-
Protein Serine-Threonine Kinases