Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0172721
Title: Identification of the ER-resident E3 ubiquitin ligase RNF145 as a novel LXR-regulated gene
Authors: Cook, Emma CL
Nelson, Jessica K
Sorrentino, Vincenzo 
Koenis, Duco
Moeton, Martina
Scheij, Saskia
Ottenhoff, Roelof
Bleijlevens, Boris
Loregger, Anke
Zelcer, Noam
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
LIVER-X-RECEPTOR
STEROL-SENSING DOMAIN
HMG COA REDUCTASE
ELEMENT-BINDING PROTEIN-1C
LIPID-METABOLISM
TRANSCRIPTION FACTORS
CHOLESTEROL EFFLUX
HUMAN MACROPHAGES
DEGRADATION
ALPHA
Issue Date: 23-Feb-2017
Publisher: PUBLIC LIBRARY SCIENCE
Citation: Cook, Emma CL, Nelson, Jessica K, Sorrentino, Vincenzo, Koenis, Duco, Moeton, Martina, Scheij, Saskia, Ottenhoff, Roelof, Bleijlevens, Boris, Loregger, Anke, Zelcer, Noam (2017-02-23). Identification of the ER-resident E3 ubiquitin ligase RNF145 as a novel LXR-regulated gene. PLOS ONE 12 (2). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0172721
Abstract: Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene. We demonstrate that RNF145 is regulated by LXRs in both human and mouse primary cells and cell lines, and in vivo in mice. Regulation of RNF145 by LXR depends on a functional LXR-element in its proximal promotor. Consistent with LXR-dependent regulation of Rnf145 we show that regulation is lost in macrophages and fibroblasts from Lxrαβ(-/-) mice, and also in vivo in livers of Lxrα(-/-) mice treated with the LXR synthetic ligand T0901317. RNF145 is closely related to RNF139/TRC8, an E3 ligase implicated in control of SREBP processing. However, silencing of RNF145 in HepG2 or HeLa cells does not impair SREBP1/2 processing and sterol-responsive gene expression in these cells. Similar to TRC8, we demonstrate that RNF145 is localized to the ER and that it possesses intrinsic E3 ubiquitin ligase activity. In summary, we report the identification of RNF145 as an ER-resident E3 ubiquitin ligase that is transcriptionally controlled by LXR.
Source Title: PLOS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/247833
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0172721
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