Publication Date:
1997-09-05
Description:
In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng et al. in this issue, serine-216 phosphorylation creates a binding site for 14-3-3 protein and inhibits function of the phosphatase. These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and mitotic entry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanchez, Y -- Wong, C -- Thoma, R S -- Richman, R -- Wu, Z -- Piwnica-Worms, H -- Elledge, S J -- GM17763/GM/NIGMS NIH HHS/ -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 Sep 5;277(5331):1497-501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9278511" target="_blank"〉PubMed〈/a〉
Keywords:
14-3-3 Proteins
;
Amino Acid Sequence
;
Animals
;
CDC2 Protein Kinase/*metabolism
;
Cell Cycle Proteins/antagonists & inhibitors/*metabolism
;
Chromosome Mapping
;
Chromosomes, Human, Pair 11
;
Cytoskeletal Proteins
;
*DNA Damage
;
*F-Box Proteins
;
G2 Phase
;
HeLa Cells
;
Humans
;
Mice
;
*Mitosis
;
Molecular Sequence Data
;
Phosphoprotein Phosphatases/metabolism
;
Phosphorylation
;
Phosphoserine/metabolism
;
Protein Kinases/chemistry/genetics/*metabolism
;
Protein Tyrosine Phosphatases/metabolism
;
Proteins/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Schizosaccharomyces pombe Proteins
;
Signal Transduction
;
Transfection
;
*Tyrosine 3-Monooxygenase
;
*Ubiquitin-Protein Ligases
;
*cdc25 Phosphatases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
