Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol
The endoplasmic reticulum enzyme 3-hydroxy-3-methylglutaryl-CoA reductase produces
mevalonate, which is converted to sterols and to other products, including geranylgeraniol
groups attached to proteins. The enzyme is known to be ubiquitinated and rapidly degraded
when sterols and nonsterol end products of mevalonate metabolism accumulate in cells.
Here, we use RNA interference to show that sterol-accelerated ubiquitination of reductase
requires Insig-1 and Insig-2, membrane-bound proteins of the endoplasmic reticulum that …
mevalonate, which is converted to sterols and to other products, including geranylgeraniol
groups attached to proteins. The enzyme is known to be ubiquitinated and rapidly degraded
when sterols and nonsterol end products of mevalonate metabolism accumulate in cells.
Here, we use RNA interference to show that sterol-accelerated ubiquitination of reductase
requires Insig-1 and Insig-2, membrane-bound proteins of the endoplasmic reticulum that …