JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint
AuthorsGutierrez, Gustavo J.
Cross, Janet V.
Davis, Roger J.
Templeton, Dennis J.
Ronai, Ze'ev A.
UMass Chan AffiliationsProgram in Molecular Medicine
Document TypeJournal Article
Fluorescent Antibody Technique
JNK Mitogen-Activated Protein Kinases
Cellular and Molecular Physiology
MetadataShow full item record
Abstractc-Jun NH(2)-terminal Kinases (JNKs) play a central role in the cellular response to a wide variety of stress signals. After their activation, JNKs induce phosphorylation of substrates, which control proliferation, migration, survival, and differentiation. Recent studies suggest that JNKs may also play a role in cell cycle control, although the underlying mechanisms are largely unexplored. Here we show that JNK directly phosphorylates Cdc25C at serine 168 during G(2) phase of the cell cycle. Cdc25C phosphorylation by JNK negatively regulates its phosphatase activity and thereby Cdk1 activation, enabling a timely control of mitosis onset. Unrestrained phosphorylation by JNK, as obtained by a cell cycle-stabilized form of JNK or as seen in some human tumors, results in aberrant cell cycle progression. Additionally, UV irradiation-induced G(2)/M checkpoint requires inactivation of Cdc25C by JNK phosphorylation. JNK phosphorylation of Cdc25C as well as Cdc25A establishes a novel link between stress signaling and unperturbed cell cycle and checkpoint pathways.
SourceJ Biol Chem. 2010 May 7;285(19):14217-28. doi: 10.1074/jbc.M110.121848. Epub 2010 Mar 10. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/28292
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