Abstract
The microphthalmia-associated transcription factor (Mitf) regulates gene expression required for osteoclast differentiation. Genes regulated by Mitf have been previously identified. However, proteins that interact and regulate Mitf's activity in osteoclasts are not well known. Here, we report that POH1, a subunit of the 19S proteasome lid is a regulator of Mitf. We show that POH1 and Mitf interact in osteoclasts and that this interaction is dependent on RANKL signaling. Overexpression of POH1 increased Mitf's activation of 5XGal4-TK and Acp5 promoters. The amino terminus of POH1 mediates the binding to Mitf and is sufficient to increase Mitf's transcriptional activity. Finally, we show that mutations in the JAMM motif of POH1 reduced Mitf activation of promoters. In summary, our results identify a novel mechanism of Mitf regulation in osteoclasts by POH1.
Copyright 2010 Wiley-Liss, Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Cell Differentiation
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Humans
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Jurkat Cells
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Macrophages / cytology
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Macrophages / metabolism
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Mice
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Microphthalmia-Associated Transcription Factor / genetics*
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Microphthalmia-Associated Transcription Factor / metabolism
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Molecular Sequence Data
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NIH 3T3 Cells
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Osteoclasts / metabolism*
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding
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Protein Processing, Post-Translational
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Protein Structure, Tertiary
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Protein Subunits / chemistry
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Protein Subunits / metabolism*
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Trans-Activators / chemistry
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Trans-Activators / metabolism*
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Transcriptional Activation / genetics*
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Two-Hybrid System Techniques
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Ubiquitination
Substances
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Microphthalmia-Associated Transcription Factor
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PSMD14 protein, mouse
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Protein Subunits
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Trans-Activators
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Proteasome Endopeptidase Complex