Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/35318
Title: Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP
Authors: Zhang, Li
Rajbhandari, Prashant
Priest, Christina
Sandhu, Jaspreet
Wu, Xiaohui
Temel, Ryan
Castrillo Viguera, Antonio 
De Aguiar Vallim, Thomas Q.
Sallam, Tamer
Tontonoz, Peter
UNESCO Clasification: 320502 Endocrinología
2407 Biología celular
3206 Ciencias de la nutrición
Keywords: Liver-X-Receptor
Cleavage-Activating protein
HMG coa reductase
LXR-Alpha
Deficient mice
Lipid-Metabolism
LDL receptor
Srebp
Gene
Pathway
Issue Date: 2017
Journal: eLife 
Abstract: Cholesterol homeostasis is maintained through concerted action of the\r\nSREBPs and LXRs. Here, we report that RNF145, a previously\r\nuncharacterized ER membrane ubiquitin ligase, participates in crosstalk\r\nbetween these critical signaling pathways. RNF145 expression is induced\r\nin response to LXR activation and high-cholesterol diet feeding.\r\nTransduction of RNF145 into mouse liver inhibits the expression of genes\r\ninvolved in cholesterol biosynthesis and reduces plasma cholesterol\r\nlevels. Conversely, acute suppression of RNF145 via shRNA-mediated\r\nknockdown, or chronic inactivation of RNF145 by genetic deletion,\r\npotentiates the expression of cholesterol biosynthetic genes and\r\nincreases cholesterol levels both in liver and plasma. Mechanistic\r\nstudies show that RNF145 triggers ubiquitination of SCAP on lysine\r\nresidues within a cytoplasmic loop essential for COPII binding,\r\npotentially inhibiting its transport to Golgi and subsequent processing\r\nof SREBP-2. These findings define an additional mechanism linking\r\nhepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR\r\npathways.
URI: http://hdl.handle.net/10553/33741
ISSN: 2050-084X
DOI: 10.7554/eLife.28766.001
Source: eLife [2050-084X], v. 6, e28766
URL: http://api.elsevier.com/content/abstract/scopus_id/85032987153
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