DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism.
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.
Department of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan. nokita7@rs.noda.tus.ac.jp
Naoyuki
N
Okita
Shota
S
Minato
Eri
E
Ohmi
Sei-ichi
S
Tanuma
Yoshikazu
Y
Higami
D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D012694:Serine; D011494:Protein Kinases; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases