Post-Translational Regulation of HMG CoA Reductase.

Mice Animals Hydroxymethylglutaryl CoA Reductases / genetics Endoplasmic Reticulum-Associated Degradation Sterols / metabolism Cholesterol / metabolism Terpenes / metabolism Dimethylallyltranstransferase / genetics

Journal

Cold Spring Harbor perspectives in biology
ISSN: 1943-0264
Titre abrégé: Cold Spring Harb Perspect Biol
Pays: United States
ID NLM: 101513680

Informations de publication

Date de publication:
01 12 2022
Historique:
pmc-release: 01 12 2024
pubmed: 9 8 2022
medline: 6 12 2022
entrez: 8 8 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1101/cshperspect.a041253 PMID: 35940903 PMC: PMC9732902
pubmed: 35940903
pii: cshperspect.a041253
doi: 10.1101/cshperspect.a041253
pmc: PMC9732902
pii:
doi:

Substances chimiques

Hydroxymethylglutaryl CoA Reductases EC 1.1.1.-
Sterols 0
Cholesterol 97C5T2UQ7J
geranylgeranyl pyrophosphate N21T0D88LX
Terpenes 0
Ubiad1 protein, mouse EC 2.5.1.1
Dimethylallyltranstransferase EC 2.5.1.1

Types de publication

Journal Article Review Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NHLBI NIH HHS
ID : P01 HL020948
Pays : United States

Informations de copyright

Copyright © 2022 Cold Spring Harbor Laboratory Press; all rights reserved.

Auteurs

Youngah Jo (Y)

Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, Texas 75390-9046, USA.

Russell A DeBose-Boyd (RA)

Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, Texas 75390-9046, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Eucaryotes › Animaux › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › 3-Hydroxyacyl-CoA dehydrogenases › Hydroxymethylglutaryl-CoA reductases › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Réponse aux protéines mal repliées › Dégradation associée au réticulum endoplasmique › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Terpènes › Post-Translational Regulation of HMG CoA Reductase.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Alkyl et aryl transferases › Dimethylallyltransferase › Post-Translational Regulation of HMG CoA Reductase.