| c-Jun N-terminal kinase/c-Jun inhibits fibroblast proliferation by negatively regulating the levels of stathmin/oncoprotein 18. | |
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MedLine Citation:
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PMID: 20594188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The JNKs (c-Jun N-terminal kinases) are stress-activated serine/threonine kinases that can regulate both cell death and cell proliferation. We have developed a cell system to control JNK re-expression at physiological levels in JNK1/2-null MEFs (murine embryonic fibroblasts). JNK re-expression restored basal and stress-activated phosphorylation of the c-Jun transcription factor and attenuated cellular proliferation with increased cells in G1/S-phase of the cell cycle. To explore JNK actions to regulate cell proliferation, we evaluated a role for the cytosolic protein, STMN (stathmin)/Op18 (oncoprotein 18). STMN, up-regulated in a range of cancer types, plays a crucial role in the control of cell division through its regulation of microtubule dynamics of the mitotic spindle. In JNK1/2-null or c-Jun-null MEFs or cells treated with c-Jun siRNA (small interfering RNA), STMN levels were significantly increased. Furthermore, a requirement for JNK/cJun signalling was demonstrated by expression of wild-type c-Jun, but not a phosphorylation-defective c-Jun mutant, being sufficient to down-regulate STMN. Critically, shRNA (small hairpin RNA)-directed STMN down-regulation in JNK1/2-null MEFs attenuated proliferation. Thus JNK/c-Jun regulation of STMN levels provides a novel pathway in regulation of cell proliferation with important implications for understanding the actions of JNK as a physiological regulator of the cell cycle and tumour suppressor protein. |
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Authors:
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Yvonne Y C Yeap; Ivan H W Ng; Bahareh Badrian; Tuong-Vi Nguyen; Yan Y Yip; Amardeep S Dhillon; Steven E Mutsaers; John Silke; Marie A Bogoyevitch; Dominic C H Ng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 430 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-13 Completed Date: 2010-09-07 Revised Date: 2010-09-22 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 345-54 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, VIC, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation* Cells, Cultured Down-Regulation* Fibroblasts / cytology*, enzymology, metabolism Mice Mice, Knockout Mitogen-Activated Protein Kinase 8 / genetics, metabolism* Mitogen-Activated Protein Kinase 9 / genetics, metabolism* Phosphorylation Proto-Oncogene Proteins c-jun / genetics, metabolism* Stathmin / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins c-jun; 0/Stathmin; EC 2.7.1.24/Mitogen-Activated Protein Kinase 9; EC 2.7.11.24/Mitogen-Activated Protein Kinase 8 |
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