Journal article
The E3 Ubiquitin Ligase gp78 Protects against ER Stress in Zebrafish Liver
Journal of genetics and genomics, Vol.41(7), pp.357-368
07/20/2014
DOI: 10.1016/j.jgg.2014.05.005
PMID: 25064675
Abstract
Enhanced endoplasmic reticulum (ER)-associated protein degradation (ERAD) activity by the unfolded protein response (UPR) represents one of the mechanisms for restoring ER homeostasis. In vitro evidence indicates that the mammalian gp78 protein is an E3 ubiquitin ligase that facilitates ERAD by polyubiquitinating and targeting proteins for proteasomal degradation under both physiologic and stress conditions. However, the in vivo function of gp78 in maintaining ER protein homeostasis remains untested. Here we show that like its mammalian counterpart, the zebrafish gp78 is also an E3 ubiquitin ligase as revealed by in vitro ubiquitination assays. Expression analysis uncovered that gp78 is highly expressed in several organs, including liver and brain, of both larval and adult fish. Treatment of larvae or adult fish with tunicamycin induces ER stress and upregulates the expression of several key components of the gp78 ERAD complex in the liver. Moreover, liver-specific overexpression of the dominant-negative form of gp78 (gp78-R2M) renders liver more sensitive to tunicamycin-induced ER stress and enhances the expression of sterol response element binding protein (Srebp)-target genes, which was largely suppressed in fish overexpressing wild-type gp78. Together, these data indicate that gp78 plays a critical role in protecting against ER stress in liver.
Details
- Title: Subtitle
- The E3 Ubiquitin Ligase gp78 Protects against ER Stress in Zebrafish Liver
- Creators
- Zhiliang Chen - University of Maryland, BaltimorePetek Ballar - Ege UniversityYu Fu - Anhui Medical UniversityJia Luo - University of KentuckyShaojun Du - University of Maryland, BaltimoreShengyun Fang - University of Maryland, Baltimore
- Resource Type
- Journal article
- Publication Details
- Journal of genetics and genomics, Vol.41(7), pp.357-368
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.jgg.2014.05.005
- PMID
- 25064675
- ISSN
- 1673-8527
- eISSN
- 1873-5533
- Language
- English
- Date published
- 07/20/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984201256202771
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