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pVHL-mediated transcriptional repression of c-Myc by recruitment of histone deacetylases

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Molecules and Cells

Abstract

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 factor1α HIF1α), thus accumulation and hyperactivation of HIF1α 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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Authors and Affiliations

  1. National Research Laboratory for Metabolic Checkpoint, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 110-799, Korea

    In-Young Hwang, Jae-Seok Roe, Hwa-Ryeon Kim & Hong-Duk Youn

  2. National Research Laboratory for Chromatin Dynamics, School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea

    Ja-Hwan Seol & Eun-Jung Cho

  3. World Class University (WCU) Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, 151-742, Korea

    Hong-Duk Youn

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  1. In-Young Hwang
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  2. Jae-Seok Roe
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  3. Ja-Hwan Seol
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  4. Hwa-Ryeon Kim
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  5. Eun-Jung Cho
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  6. Hong-Duk Youn
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Correspondence to Eun-Jung Cho or Hong-Duk Youn.

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Hwang, IY., Roe, JS., Seol, JH. et al. pVHL-mediated transcriptional repression of c-Myc by recruitment of histone deacetylases. Mol Cells 33, 195–201 (2012). https://doi.org/10.1007/s10059-012-2268-3

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  • DOI: https://doi.org/10.1007/s10059-012-2268-3

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