Statin therapy inhibits fatty acid synthase via dynamic protein modifications.
Statin therapy inhibits fatty acid synthase via dynamic protein modifications.
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DOI：
10.1038/s41467-022-30060-w
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发表时间：
2022-05-10
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we observe a strong increase in HMG-CoA levels and modification of only a single protein. Mass spectrometry identifies this protein as fatty acid synthase (FAS), which is modified on active site residues and, importantly, on non-lysine side-chains. The dynamic modifications occur only on a sub-pool of FAS that is located near HMGCR and alters cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner. Statin therapy is associated with numerous cellular effects. Here, the authors show that statin treatment increases post-translational modifications on fatty acid synthase in the active site, revealing communication between the cholesterol and lipid biosynthetic pathways.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.4
作者：
Meier, Jordan L.;Patel, Anand D.;Niessen, Sherry;Meehan, Michael;Kersten, Roland;Yang, Jane Y.;Rothmann, Michael;Cravatt, Benjamin F.;Dorrestein, Pieter C.;Burkart, Michael D.;Bafna, Vineet
通讯作者：
Bafna, Vineet
影响因子：
3.5
作者：
CARLING, D;ZAMMIT, VA;HARDIE, DG
通讯作者：
HARDIE, DG
影响因子：
6.5
作者：
Jensen-Urstad, Anne P. L.;Song, Haowei;Semenkovich, Clay F.
通讯作者：
Semenkovich, Clay F.