1. Academic Validation
  2. Sirt1 deacetylates c-Myc and promotes c-Myc/Max association

Sirt1 deacetylates c-Myc and promotes c-Myc/Max association

  • Int J Biochem Cell Biol. 2011 Nov;43(11):1573-81. doi: 10.1016/j.biocel.2011.07.006.
Beibei Mao 1 Guowei Zhao Xiang Lv Hou-Zao Chen Zheng Xue Ben Yang De-Pei Liu Chih-Chuan Liang
Affiliations

Affiliation

  • 1 National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Abstract

The c-Myc oncoprotein plays critical roles in multiple biological processes by controlling cell proliferation, Apoptosis, differentiation, and metabolism. Especially, c-Myc is frequently overexpressed in many human cancers and widely involved in tumorigenesis. However, how the post-translational modifications, especially acetylation of c-Myc, contribute to its activity in the leukemia cells remains largely unknown. SIRT1, a NAD-dependent class III histone deacetylase, has a paradoxical role in tumorigenesis by deacetylating several transcription factors, including p53, E2F1 and forkhead proteins. In this study, we show that SIRT1 interacts physically with the C-terminus of c-Myc and deacetylates c-Myc both in vitro and in vivo. Moreover, the deacetylation of c-Myc by SIRT1 promotes its association with Max, a partner essential for its activation, thereby facilitating c-Myc transactivation activity on hTERT promoter. Finally, inhibition of endogenous SIRT1 in K562 cells by either RNAi or its inhibitor NAM causes the overall decrease of c-Myc target genes expression, including hTERT, cyclinD2 and LDHA, which further suppress cell proliferation and arrest cell cycle at G1/S phase. Thus, our results demonstrate the positive effect of SIRT1 on c-Myc activity by efficiently enhancing c-Myc/Max association in human leukemia cell line K562, suggesting a potential role of SIRT1 in tumorigenesis.

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