HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 6, 4894-4905, February 11, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/6/4894    most recent M411894200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, X. Articles by Friedman, E. Search for Related Content PubMed PubMed Citation Articles by Deng, X. Articles by Friedman, E. Social Bookmarking                      What's this?

Mirk/dyrk1B Decreases the Nuclear Accumulation of Class II Histone Deacetylases during Skeletal Muscle Differentiation^*

Xiaobing Deng, Daina Z. Ewton, Stephen E. Mercer, and Eileen Friedman

From the Department of Pathology, Upstate Medical University, State University of New York, Syracuse, New York 13210

Mirk/dyrk1B is a member of the dyrk/minibrain family of serine/threonine kinases that mediate the transition from growth to differentiation in lower eukaryotes and mammals. Depletion of endogenous Mirk from C2C12 myoblasts by RNA interference blocks skeletal muscle differentiation (Deng, X., Ewton, D., Pawlikowski, B., Maimone, M., and Friedman, E. (2003) J. Biol. Chem. 278, 41347-41354). We now demonstrate that knockdown of Mirk blocks transcription of the muscle regulatory factor myogenin. Co-expression of Mirk with MEF2C, but not MyoD or Myf5, enhanced activation of the myogenin promoter in a Mirk kinase-dependent manner. Mirk activated MEF2 not through direct phosphorylation of MEF2 but by phosphorylation of its inhibitors, the class II histone deacetylases (HDACs). MEF2 is sequestered by class II HDACs such as HDAC5 and MEF2-interacting transcriptional repressor (MITR). Mirk antagonized the inhibition of MEF2C by MITR, whereas kinase-inactive Mirk was ineffective. Mirk phosphorylates class II HDACs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner. Moreover, less mutant MITR phosphomimetic at the Mirk phosphorylation site localized in the nucleus than wild-type MITR. Regulation of class II HDACs occurs by multiple mechanisms. Others have shown that calcium signaling leads to phosphorylation of HDACs at 14-3-3-binding sites, blocking their association with MEF2 within the nucleus. Mirk provides another level of regulation. Mirk is induced within the initial 24 h of myogenic differentiation and enables MEF2 to transcribe the myogenin gene by decreasing the nuclear accumulation of class II HDACs.

Received for publication, October 20, 2004

^* This work was supported by United States Public Health Service Award RO1 CA67405 (to E. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Upstate Medical University, Pathology Dept., 2303 Weiskotten Hall, 750 East Adams St., Syracuse, NY 13210. Tel.: 315-464-7138; Fax: 315-464-8419; E-mail: friedmae{at}upstate.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. L. S. Perry, C. Yang, N. Soora, J. Salma, M. Marback, L. Naghibi, H. Ilyas, J. Chan, J. W. Gordon, and J. C. McDermott Direct Interaction between Myocyte Enhancer Factor 2 (MEF2) and Protein Phosphatase 1{alpha} Represses MEF2-Dependent Gene Expression Mol. Cell. Biol., June 15, 2009; 29(12): 3355 - 3366. [Abstract] [Full Text] [PDF]

				X. Deng, D. Z. Ewton, and E. Friedman Mirk/Dyrk1B Maintains the Viability of Quiescent Pancreatic Cancer Cells by Reducing Levels of Reactive Oxygen Species Cancer Res., April 15, 2009; 69(8): 3317 - 3324. [Abstract] [Full Text] [PDF]

				A. Margariti, Q. Xiao, A. Zampetaki, Z. Zhang, H. Li, D. Martin, Y. Hu, L. Zeng, and Q. Xu Splicing of HDAC7 modulates the SRF-myocardin complex during stem-cell differentiation towards smooth muscle cells J. Cell Sci., February 15, 2009; 122(4): 460 - 470. [Abstract] [Full Text] [PDF]

				A. M. Craft, D. M. Krisky, J. B. Wechuck, E. K. Lobenhofer, Y. Jiang, D. P. Wolfe, and J. C. Glorioso Herpes Simplex Virus-Mediated Expression of Pax3 and MyoD in Embryoid Bodies Results in Lineage-Related Alterations in Gene Expression Profiles Stem Cells, December 1, 2008; 26(12): 3119 - 3129. [Abstract] [Full Text] [PDF]

				K. Jin, S. Park, D. Z. Ewton, and E. Friedman The Survival Kinase Mirk/Dyrk1B Is a Downstream Effector of Oncogenic K-ras in Pancreatic Cancer Cancer Res., August 1, 2007; 67(15): 7247 - 7255. [Abstract] [Full Text] [PDF]

				L. G. Puente, S. Voisin, R. E. C. Lee, and L. A. Megeney Reconstructing the Regulatory Kinase Pathways of Myogenesis from Phosphopeptide Data Mol. Cell. Proteomics, December 1, 2006; 5(12): 2244 - 2251. [Abstract] [Full Text] [PDF]

				S. E. Mercer, D. Z. Ewton, S. Shah, A. Naqvi, and E. Friedman Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. Cancer Res., May 15, 2006; 66(10): 5143 - 5150. [Abstract] [Full Text] [PDF]

				X. Deng, D. Z. Ewton, S. Li, A. Naqvi, S. E. Mercer, S. Landas, and E. Friedman The Kinase Mirk/Dyrk1B Mediates Cell Survival in Pancreatic Ductal Adenocarcinoma. Cancer Res., April 15, 2006; 66(8): 4149 - 4158. [Abstract] [Full Text] [PDF]

				S. E. Mercer, D. Z. Ewton, X. Deng, S. Lim, T. R. Mazur, and E. Friedman Mirk/Dyrk1B Mediates Survival during the Differentiation of C2C12 Myoblasts J. Biol. Chem., July 8, 2005; 280(27): 25788 - 25801. [Abstract] [Full Text] [PDF]