JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint
Authors
Gutierrez, Gustavo J.Tsuji, Toshiya
Cross, Janet V.
Davis, Roger J.
Templeton, Dennis J.
Jiang, Wei
Ronai, Ze'ev A.
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2010-05-07Keywords
AnimalsBlotting, Western
Cell Division
Cell Proliferation
Cells, Cultured
*DNA Damage
Fluorescent Antibody Technique
G2 Phase
Humans
JNK Mitogen-Activated Protein Kinases
Mice
Mitosis
Phosphorylation
cdc25 Phosphatases
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
Metadata
Show full item recordAbstract
c-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.Source
J 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 siteDOI
10.1074/jbc.M110.121848Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28292PubMed ID
20220133Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M110.121848