Oncotarget

Research Papers:

Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases

Ying Wang _, Seung-Wook Ha, Tianpeng Zhang, Dhong-Hyo Kho, Avraham Raz and Youming Xie

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Oncotarget. 2014; 5:2044-2051. https://doi.org/10.18632/oncotarget.1478

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Abstract

Ying Wang1,*, Seung-Wook Ha1,*, Tianpeng Zhang1,*, Dhong-Hyo Kho1, Avraham Raz1, and Youming Xie1

1 Barbara Ann Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA

* These authors contributed equally to the work

Correspondence:

Avraham Raz, email:

Youming Xie, email:

Keywords: protein ubiquitylation, ubiquitin ligase, AMF, gp78, TRIM25

Received: October 8, 2013 Accepted: October 27, 2013 Published: October 28, 2013

Abstract

gp78 is a ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD). Here we report that autocrine motility factor (AMF), also known as phosphoglucose isomerase (PGI), is a novel substrate of gp78. We show that polyubiquitylation of AMF requires cooperative interaction between gp78 and the ubiquitin ligase TRIM25 (tripartite motif-containing protein 25). While TRIM25 mediates the initial round of ubiquitylation, gp78 catalyzes polyubiquitylation of AMF. The E4-like activity of gp78 was illustrated by an in vitro polyubiquitylation assay using Ub-DHFR as a model substrate. We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78. This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation.


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