QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 9, 3897-3906, September 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-05-0470v1 17/9/3897    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bronisz, A. Articles by Ostrowski, M. C. Search for Related Content PubMed PubMed Citation Articles by Bronisz, A. Articles by Ostrowski, M. C.

Microphthalmia-associated Transcription Factor Interactions with 14-3-3 Modulate Differentiation of Committed Myeloid Precursors

Agnieszka Bronisz^*, Sudarshana M. Sharma^*, Rong Hu^*, Jakub Godlewski, Guri Tzivion, Kim C. Mansky, and Michael C. Ostrowski^*

*Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center, and Department of Neurological Surgery, The Dardinger Family Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Medical Center, Columbus, OH 43210; Karmanos Cancer Institute and Department of Pathology, Wayne State University, Detroit, MI 48201; and Division of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455

Submitted May 31, 2006; Revised June 22, 2006; Accepted June 23, 2006
Monitoring Editor: Marianne Bronner-Fraser

The microphthalmia-associated transcription factor (MITF) is required for terminal osteoclast differentiation and is a target for signaling pathways engaged by colony stimulating factor (CSF)-1 and receptor-activator of nuclear factor-B ligand (RANKL). Work presented here demonstrates that MITF can shuttle from cytoplasm to nucleus dependent upon RANKL/CSF-1 action. 14-3-3 was identified as a binding partner of MITF in osteoclast precursors, and overexpression of 14-3-3 in a transgenic model resulted in increased cytosolic localization of MITF and decreased expression of MITF target genes. MITF/14-3-3 interaction was phosphorylation dependent, and Ser173 residue, within the minimal interaction region of amino acid residues 141–191, was required. The Cdc25C-associated kinase (C-TAK)1 interacted with an overlapping region of MITF. C-TAK1 increased MITF/14-3-3 complex formation and thus promoted cytoplasmic localization of MITF. C-TAK1 interaction was disrupted by RANKL/CSF-1 treatment. The results indicate that 14-3-3 regulates MITF activity by promoting the cytosolic localization of MITF in the absence of signals required for osteoclast differentiation. This work identifies a mechanism that regulates MITF activity in monocytic precursors that are capable of undergoing different terminal differentiation programs, and it provides a mechanism that allows committed precursors to rapidly respond to signals in the bone microenvironment to promote specifically osteoclast differentiation.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-05-0470) on July 5, 2006.

Address correspondence to: Michael C. Ostrowski (michael.ostrowski{at}osumc.edu)

This article has been cited by other articles:

				R. Hu, S. M. Sharma, A. Bronisz, R. Srinivasan, U. Sankar, and M. C. Ostrowski Eos, MITF, and PU.1 Recruit Corepressors to Osteoclast-Specific Genes in Committed Myeloid Progenitors Mol. Cell. Biol., June 1, 2007; 27(11): 4018 - 4027. [Abstract] [Full Text] [PDF]

				S. M. Sharma, A. Bronisz, R. Hu, K. Patel, K. C. Mansky, S. Sif, and M. C. Ostrowski MITF and PU.1 Recruit p38 MAPK and NFATc1 to Target Genes during Osteoclast Differentiation J. Biol. Chem., May 25, 2007; 282(21): 15921 - 15929. [Abstract] [Full Text] [PDF]