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KMID : 0578320120330020195
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Molecules and Cells
2012 Volume.33 No. 2 p.195 ~ p.201
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pVHL-Mediated Transcriptional Repression of c-Myc by Recruitment of Histone Deacetylases
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Hwang In-Young
Roe Jae-Seok
Seol Ja-Hwan
Kim Hwa-Ryeon
Cho Eun-Jung
Youn Hong-Duk
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Abstract
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The biological functions of Myc are to regulate cell growth, apoptosis, cell differentiation and stem-cell self-renewal. Abnormal accumulation of c-Myc is able to induce excessive proliferation of normal cells. von Hippel-Lindau protein (pVHL) is a key regulator of hypoxia-inducible factor1? (HIF1?), thus accumulation and hyperactivation of HIF1? is the most prominent feature of VHL-mutated renal cell carcinoma. Interestingly, the Myc pathway is reported to be activated in renal cell carcinoma even though the precise molecular mechanism still remains to be established. Here, we demonstrated that pVHL locates at the c-Myc promoter region through physical interaction with Myc. Furthermore, pVHL reinforces HDAC1/2 recruitment to the Myc promoter, which leads to the auto-suppression of Myc. Therefore, one possible mechanism of Myc auto-suppression by pVHL entails removing histone acetylation. Our study identifies a novel mechanism for pVHL-mediated negative regulation of c-Myc transcription.
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KEYWORD
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c-Myc, histone deacetylase (HDAC), renal cell carcinoma (RCC), von Hippel-Lindau (VHL)
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