Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print July 5, 2006
Mol. Biol. Cell 10.1091/mbc.E06-05-0470

A more recent version of this article appeared on September 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E06-05-0470v1
17/9/3897    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bronisz, A.
Right arrow Articles by Ostrowski, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bronisz, A.
Right arrow Articles by Ostrowski, M. C.

Submitted on May 31, 2006
Revised on June 22, 2006
Accepted on June 23, 2006

MITF Interactions with 14-3-3 Modulate Differentiation of Committed Myeloid Precursors

Agnieszka Bronisz,* Sudarshana M. Sharma,* Rong Hu,* Jakub Godlewski,{dagger} Guri Tzivion,{ddagger} Kim C. Mansky,{sect} and Michael C. Ostrowski*

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

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-1 (CSF-1) and Receptor-Activator of NF-{kappa}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 serine residue 173, within the minimal interaction region of amino acid residues 141-191, was required. The Cdc25C-associated kinase 1 (C-TAK1) 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 provides a mechanism that allows committed precursors to rapidly respond to signals in the bone microenvironment to promote specifically osteoclast differentiation.

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




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
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]

Home page
 J. Biol. Chem.Home page
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]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2006 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.