DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism

► Ser296 phosphorylation of CHK1 is regulated by an ATR-dependent pathway. ► CHK1 autophosphorylates at Ser296 via an intramolecular mechanism. ► Ser296 cis-autophosphorylation is dependent on Ser317 and Ser345 phosphorylation. CHK1 regulates the DNA damage-induced checkpoint involving an ATR- or AT...

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Bibliographic Details
Published in:FEBS letters 2012-11, Vol.586 (22), p.3974-3979
Main Authors: Okita, Naoyuki, Minato, Shota, Ohmi, Eri, Tanuma, Sei-ichi, Higami, Yoshikazu
Format: Article
Language:English
Subjects:
Ataxia Telangiectasia Mutated Proteins
ATR
Blotting, Western
Cell Cycle Checkpoints
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Checkpoint Kinase 1
CHK1
cis-Autophosphorylation
DNA Damage
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
HeLa Cells
Humans
Kinase
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
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Summary:► Ser296 phosphorylation of CHK1 is regulated by an ATR-dependent pathway. ► CHK1 autophosphorylates at Ser296 via an intramolecular mechanism. ► Ser296 cis-autophosphorylation is dependent on Ser317 and Ser345 phosphorylation. 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. CHK1phosphorylatesCHK1 by protein kinase assay (View Interaction: 1, 2, 3)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2012.09.048