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Mol. Cells 2012; 33(2): 195-201

Published online February 29, 2012

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

© The Korean Society for Molecular and Cellular Biology

pVHL-Mediated Transcriptional Repression of c-Myc by Recruitment of Histone Deacetylases

In-Young Hwang1, Jae-Seok Roe1, Ja-Hwan Seol2, Hwa-Ryeon Kim1, Eun-Jung Cho2,*, and Hong-Duk Youn1,3,*

1National Research Laboratory for Metabolic Checkpoint, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea, 2National Research Laboratory for Chromatin Dynamics, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea, 3World Class University (WCU) Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 151-742, Korea

Correspondence to : *Correspondence: hdyoun@snu.ac.kr (HDY); echo@skku.edu (EJC)

Received: November 23, 2011; Accepted: November 29, 2011

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 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.

Keywords c-Myc, histone deacetylase (HDAC), renal cell carcinoma (RCC), von Hippel-Lindau (VHL)

Article

Research Article

Mol. Cells 2012; 33(2): 195-201

Published online February 29, 2012 https://doi.org/10.1007/s10059-012-2268-3

Copyright © The Korean Society for Molecular and Cellular Biology.

pVHL-Mediated Transcriptional Repression of c-Myc by Recruitment of Histone Deacetylases

In-Young Hwang1, Jae-Seok Roe1, Ja-Hwan Seol2, Hwa-Ryeon Kim1, Eun-Jung Cho2,*, and Hong-Duk Youn1,3,*

1National Research Laboratory for Metabolic Checkpoint, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea, 2National Research Laboratory for Chromatin Dynamics, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea, 3World Class University (WCU) Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 151-742, Korea

Correspondence to:*Correspondence: hdyoun@snu.ac.kr (HDY); echo@skku.edu (EJC)

Received: November 23, 2011; Accepted: November 29, 2011

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 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.

Keywords: c-Myc, histone deacetylase (HDAC), renal cell carcinoma (RCC), von Hippel-Lindau (VHL)

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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