| Literature DB >> 27758890 |
Huai-Peng Lin1,2,3, Zhou-Li Cheng1,2,3, Ruo-Yu He4, Lei Song5, Meng-Xin Tian6,7, Li-Sha Zhou1,2,3, Beezly S Groh8, Wei-Ren Liu6,7, Min-Biao Ji4, Chen Ding1,2,3,5, Ying-Hong Shi6,7, Kun-Liang Guan9,2,3,10, Dan Ye9,2,3,11, Yue Xiong9,2,3,8.
Abstract
Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacologic inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity, and other diseases. Here, we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels. Our results suggest opportunities to target FASN acetylation as an anticancer strategy. Cancer Res; 76(23); 6924-36. ©2016 AACR. ©2016 American Association for Cancer Research.Entities:
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Year: 2016 PMID： 27758890 PMCID： PMC5135623 DOI： 10.1158/0008-5472.CAN-16-1597
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701