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

• Published in: Molecules and cells Vol. 33; no. 2; pp. 195 - 201
• Main Authors: Hwang, I.Y., Seoul National University College of Medicine, Seoul, Republic of Korea, Roe, J.S., Seoul National University College of Medicine, Seoul, Republic of Korea, Seol, J.H., Sungkyunkwan University, Suwon, Republic of Korea, Kim, H.R., Seoul National University College of Medicine, Seoul, Republic of Korea, Cho, E.J., Sungkyunkwan University, Suwon, Republic of Korea, Youn, H.D., Seoul National University College of Medicine, Seoul, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.02.2012; Korea Society for Molecular and Cellular Biology; 한국분자세포생물학회
• Subjects: Acetylation; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Carcinoma, Renal Cell - enzymology; Carcinoma, Renal Cell - genetics; Cell Biology; Cell Proliferation; CELLS; CELLULE; CELULAS; Gene Expression Regulation, Neoplastic; HEK293 Cells; histone deacetylase; Histone Deacetylases - metabolism; Homeostasis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Kidney Neoplasms - enzymology; Kidney Neoplasms - genetics; Life Sciences; Promoter Regions, Genetic - genetics; Protein Binding; Proto-Oncogene Proteins c-myc - genetics; renal cell carcinoma; Response Elements - genetics; Sequence Deletion - genetics; Transcriptional Activation - genetics; von Hippel-Lindau; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Von Hippel-Lindau Tumor Suppressor Protein - metabolism; 생물학; von Hippel-Lindau (VHL); histone deacetylase (HDAC); c-Myc; renal cell carcinoma (RCC)
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-012-2268-3

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.