| Literature DB >> 32694775 |
Shi-Ting Li1, Shengqi Shen1, Yongping Cai2, Songge Xing1, Gongwei Wu1, Zetan Jiang1, Yijie Hao1, Mengqiu Yuan1,3,4, Nana Wang2, Lianbang Zhu1, Ronghui Yan1, Dongdong Yang1, Lin Wang1, Zhaoji Liu1,3,4, Xin Hu1, Rongbin Zhou1, Kun Qu1, Ailing Li5, Xiaotao Duan6, Huafeng Zhang7, Ping Gao8,9,10,11.
Abstract
The transcriptional role of cMyc (or Myc) in tumorigenesis is well appreciated; however, it remains to be fully established how extensively Myc is involved in the epigenetic regulation of gene expression. Here, we show that by deactivating succinate dehydrogenase complex subunit A (SDHA) via acetylation, Myc triggers a regulatory cascade in cancer cells that leads to H3K4me3 activation and gene expression. We find that Myc facilitates the acetylation-dependent deactivation of SDHA by activating the SKP2-mediated degradation of SIRT3 deacetylase. We further demonstrate that Myc inhibition of SDH-complex activity leads to cellular succinate accumulation, which triggers H3K4me3 activation and tumour-specific gene expression. We demonstrate that acetylated SDHA at Lys 335 contributes to tumour growth in vitro and in vivo, and we confirm increased tumorigenesis in clinical samples. This study illustrates a link between acetylation-dependent SDHA deactivation and Myc-driven epigenetic regulation of gene expression, which is critical for cancer progression.Entities:
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Year: 2020 PMID： 32694775 DOI： 10.1038/s42255-020-0179-8
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812