Current Protein & Peptide Science

Ben M. Dunn  
Department of Biochemistry and Molecular Biology University of Florida
College of Medicine, P.O. Box 100245, Gainesville
Florida, FL 32610-0245


gp78: a Multifaceted Ubiquitin Ligase that Integrates a Unique Protein Degradation Pathway from the Endoplasmic Reticulum

Author(s): Zhiliang Chen, Shaojun Du and Shengyun Fang

Affiliation: Center for Biomedical Engineering and Technology, Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.


The endoplasmic reticulum (ER) is the site for maturation of proteins destined for the secretory pathway. Failure in maturation leads to production of misfolded proteins that are eliminated through the ER-associated degradation (ERAD) pathway. ERAD is a complex process that includes misfolded protein recognition, retrotranslocation to the cytosol, ubiquitination and proteasomal degradation. gp78 is an E3 ubiquitin ligase that integrates these ERAD steps by nucleating a unique degradation machine, which uses the p97/VCP-Npl4 complex for retrotranslocation instead of the wellknown p97/VCP-Ufd1-Npl4 complex. A growing list of substrates have been identified for gp78, which highlights the importance of gp78-mediated ERAD in essential physiological pathways and pathological processes.

Keywords: ubiquitination, retrotranslocation/dislocation, E3 ubiquitin ligase, gp78, Hrd1, p97/VCP, proteasome, endoplasmic reticulum, and ER-associated degradation

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Article Details

Page: [414 - 424]
Pages: 11
DOI: 10.2174/138920312802430590