| Autor: |
Matthew D. Hirschey, Thompson Jw, Scott B. Crown, Paul A. Grimsrud, Robert Stevens, Gregory R. Wagner, Trub A, Donald S. Backos, Olga Ilkayeva, Zhang G |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-465103/v1 |
| Popis: |
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 reactive HMG-CoA into mevalonate. Recent discoveries revealed HMG-CoA is a highly reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins would increase HMG-CoA levels and subsequent protein modifications. We found a strong increase in HMG-CoA levels, but only a single protein being modified. Fatty acid synthase (FAS) was modified on active site residues and, importantly, the modification is located on non-lysine residues. The dynamic modifications occur only on a subpool 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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