Post-Translational Regulation of HMG CoA Reductase.
Cold Spring Harb Perspect Biol
; 14(12)2022 12 01.
Article
en En
| MEDLINE
| ID: mdl-35940903
ABSTRACT
3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an endoplasmic reticulum (ER)-localized integral membrane protein that catalyzes the rate-limiting step in the synthesis of cholesterol and many nonsterol isoprenoids including geranylgeranyl pyrophosphate (GGpp). HMGCR is subjected to strict feedback control through multiple mechanisms to ensure cells constantly produce essential nonsterol isoprenoids, but do not overaccumulate cholesterol. Here, we focus on the mechanism of feedback control of HMGCR that involves its sterol-induced ubiquitination and ER-associated degradation (ERAD) that is augmented by GGpp. We will also discuss the how GGpp-regulated intracellular trafficking of the vitamin K2 synthetic enzyme UbiA prenyltransferase domain-containing protein-1 (UBIAD1) inhibits HMGCR ERAD to balance the synthesis of sterol and nonsterol isoprenoids. Finally, we will summarize various mouse models, the characterization of which establish that sterol-accelerated, UBIAD1-modulated ERAD plays a major role in regulation of HMGCR and cholesterol metabolism in vivo.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Dimetilaliltranstransferasa
/
Hidroximetilglutaril-CoA Reductasas
Idioma:
En
Revista:
Cold Spring Harb Perspect Biol
Asunto de la revista:
BIOLOGIA
Año:
2022
Tipo del documento:
Article