Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
Human Cdc25C is a dual-specificity protein phosphatase that controls entry into mitosis by dephosphorylating the protein kinase Cdc2. Throughout interphase, but not in mitosis, Cdc25C was phosphorylated on serine-216 and bound to members of the highly conserved and ubiquitously expressed family of 14-3-3 proteins. A mutation preventing phosphorylation of serine-216 ... abrogated 14-3-3 binding. Conditional overexpression of this mutant perturbed mitotic timing and allowed cells to escape the G2 checkpoint arrest induced by either unreplicated DNA or radiation-induced damage. Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-216. These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells.
Mesh Terms:
14-3-3 Proteins, Amino Acid Sequence, Cell Cycle Proteins, DNA Damage, DNA Replication, G2 Phase, Gamma Rays, Hela Cells, Humans, Jurkat Cells, Mitosis, Molecular Sequence Data, Mutation, Phosphorylation, Phosphoserine, Protein Kinases, Proteins, Recombinant Fusion Proteins, S Phase, Tyrosine 3-Monooxygenase, cdc25 Phosphatases
14-3-3 Proteins, Amino Acid Sequence, Cell Cycle Proteins, DNA Damage, DNA Replication, G2 Phase, Gamma Rays, Hela Cells, Humans, Jurkat Cells, Mitosis, Molecular Sequence Data, Mutation, Phosphorylation, Phosphoserine, Protein Kinases, Proteins, Recombinant Fusion Proteins, S Phase, Tyrosine 3-Monooxygenase, cdc25 Phosphatases
Science
Date: Sep. 05, 1997
PubMed ID: 9278512
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