| Nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts. | |
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MedLine Citation:
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PMID: 17488950 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nucleus contains diacylglycerol kinases (DGKs), i.e., the enzymes that, by converting diacylglycerol (DG) into phosphatidic acid, terminate DG-dependent events. It has been demonstrated that nuclear DGK-zeta interferes with cell cycle progression. We previously reported that nuclear DGK-zeta expression increased during myogenic differentiation, whereas its down-regulation impaired differentiation. Here, we evaluated the possible involvement of nuclear DGK-zeta in cell cycle progression of C2C12 myoblasts. Overexpression of a wild-type DGK-zeta, which mainly localized to the nucleus (but not of a kinase dead mutant or of a mutant that did not enter the nucleus), blocked the cells in the G1 phase of the cell cycle, as demonstrated by in situ analysis of biotinylated-16-dUTP incorporated into newly synthesized DNA and by flow cytometry. In contrast, down-regulation of endogenous DGK-zeta by short interfering RNA (siRNA) increased the number of cells in both the S and G2/M phases of the cell cycle. Cell cycle arrest of cells overexpressing wild-type DGK-zeta was accompanied by decreased levels of retinoblastoma protein phosphorylated on Ser-807/811. Down-regulation of endogenous DGK-zeta, using siRNA, prevented the cell cycle block characterizing C2C12 cell myogenic differentiation. Overall, our results identify nuclear DGK-zeta as a key determinant of cell cycle progression and differentiation of C2C12 cells. |
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Authors:
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Camilla Evangelisti; Pier Luigi Tazzari; Massimo Riccio; Roberta Fiume; Yasukazu Hozumi; Federica Falà; Kaoru Goto; Lucia Manzoli; Lucio Cocco; Alberto M Martelli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-08 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 21 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-10-01 Completed Date: 2008-01-07 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 3297-307 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Cell Signalling Laboratory, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / physiology* Cell Cycle Proteins / metabolism Cell Differentiation* Cell Line Cell Nucleus / enzymology* DNA Replication Diacylglycerol Kinase / genetics, metabolism* Isoenzymes / genetics, metabolism* Mice Myoblasts* / cytology, enzymology, physiology RNA, Small Interfering / genetics, metabolism Recombinant Fusion Proteins / genetics, metabolism Retinoblastoma Protein / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Isoenzymes; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 0/Retinoblastoma Protein; EC 2.7.1.107/Diacylglycerol Kinase; EC 2.7.1.107/diacylglycerol kinase zeta, mouse |
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