Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1

UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4. The prenyltransferase has emerged as a key regulator of sterol-accelerated, endoplasmic reticulum (ER)-associated degradation (ERAD) of HMG CoA...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rania Elsabrouty, Youngah Jo, Seonghwan Hwang, Dong-Jae Jun, Russell A DeBose-Boyd
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	vesicular transport cholesterol metabolism isoprenoids ER-associated degradation prenylation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7cd4aab5f3a242ce97aaefc96cbb2e1e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7cd4aab5f3a242ce97aaefc96cbb2e1e
record_format	dspace
spelling	oai:doaj.org-article:7cd4aab5f3a242ce97aaefc96cbb2e1e2021-12-03T15:43:18ZType 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD110.7554/eLife.646882050-084Xe64688https://doaj.org/article/7cd4aab5f3a242ce97aaefc96cbb2e1e2021-11-01T00:00:00Zhttps://elifesciences.org/articles/64688https://doaj.org/toc/2050-084XUbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4. The prenyltransferase has emerged as a key regulator of sterol-accelerated, endoplasmic reticulum (ER)-associated degradation (ERAD) of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids including GGpp. Sterols induce binding of UBIAD1 to reductase, inhibiting its ERAD. Geranylgeraniol (GGOH), the alcohol derivative of GGpp, disrupts this binding and thereby stimulates ERAD of reductase and translocation of UBIAD1 to Golgi. We now show that overexpression of Type 1 polyisoprenoid diphosphate phosphatase (PDP1), which dephosphorylates GGpp and other isoprenyl pyrophosphates to corresponding isoprenols, abolishes protein geranylgeranylation as well as GGOH-induced ERAD of reductase and Golgi transport of UBIAD1. Conversely, these reactions are enhanced in the absence of PDP1. Our findings indicate PDP1-mediated hydrolysis of GGpp significantly contributes to a feedback mechanism that maintains optimal intracellular levels of the nonsterol isoprenoid.Rania ElsabroutyYoungah JoSeonghwan HwangDong-Jae JunRussell A DeBose-BoydeLife Sciences Publications Ltdarticlevesicular transportcholesterol metabolismisoprenoidsER-associated degradationprenylationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vesicular transport cholesterol metabolism isoprenoids ER-associated degradation prenylation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	vesicular transport cholesterol metabolism isoprenoids ER-associated degradation prenylation Medicine R Science Q Biology (General) QH301-705.5 Rania Elsabrouty Youngah Jo Seonghwan Hwang Dong-Jae Jun Russell A DeBose-Boyd Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
description	UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4. The prenyltransferase has emerged as a key regulator of sterol-accelerated, endoplasmic reticulum (ER)-associated degradation (ERAD) of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids including GGpp. Sterols induce binding of UBIAD1 to reductase, inhibiting its ERAD. Geranylgeraniol (GGOH), the alcohol derivative of GGpp, disrupts this binding and thereby stimulates ERAD of reductase and translocation of UBIAD1 to Golgi. We now show that overexpression of Type 1 polyisoprenoid diphosphate phosphatase (PDP1), which dephosphorylates GGpp and other isoprenyl pyrophosphates to corresponding isoprenols, abolishes protein geranylgeranylation as well as GGOH-induced ERAD of reductase and Golgi transport of UBIAD1. Conversely, these reactions are enhanced in the absence of PDP1. Our findings indicate PDP1-mediated hydrolysis of GGpp significantly contributes to a feedback mechanism that maintains optimal intracellular levels of the nonsterol isoprenoid.
format	article
author	Rania Elsabrouty Youngah Jo Seonghwan Hwang Dong-Jae Jun Russell A DeBose-Boyd
author_facet	Rania Elsabrouty Youngah Jo Seonghwan Hwang Dong-Jae Jun Russell A DeBose-Boyd
author_sort	Rania Elsabrouty
title	Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
title_short	Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
title_full	Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
title_fullStr	Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
title_full_unstemmed	Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1
title_sort	type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of hmg coa reductase and ubiad1
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/7cd4aab5f3a242ce97aaefc96cbb2e1e
work_keys_str_mv	AT raniaelsabrouty type1polyisoprenoiddiphosphatephosphatasemodulatesgeranylgeranylmediatedcontrolofhmgcoareductaseandubiad1 AT youngahjo type1polyisoprenoiddiphosphatephosphatasemodulatesgeranylgeranylmediatedcontrolofhmgcoareductaseandubiad1 AT seonghwanhwang type1polyisoprenoiddiphosphatephosphatasemodulatesgeranylgeranylmediatedcontrolofhmgcoareductaseandubiad1 AT dongjaejun type1polyisoprenoiddiphosphatephosphatasemodulatesgeranylgeranylmediatedcontrolofhmgcoareductaseandubiad1 AT russelladeboseboyd type1polyisoprenoiddiphosphatephosphatasemodulatesgeranylgeranylmediatedcontrolofhmgcoareductaseandubiad1
_version_	1718373155933782016

Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1

Ejemplares similares