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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lin HP,Cheng ZL,He RY,Song L,Tian MX,Zhou LS,Groh BS,Liu WR,Ji MB,Ding C,Shi YH,Guan KL,Ye D,Xiong Ydoi
10.1158/0008-5472.CAN-16-1597subject
Has Abstractpub_date
2016-12-01 00:00:00pages
6924-6936issue
23eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-1597journal_volume
76pub_type
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