Characterization of the deubiquitinating activity of USP19 and its role in endoplasmic reticulum-associated degradation.

The Journal of Biological Chemistry
Jin-gu LeeYihong Ye

Abstract

Deubiquitinating enzymes (DUBs) regulate various cellular processes ranging from protein degradation to cellular signaling. USP19, the only DUB containing a carboxyl-terminal transmembrane domain, was proposed to function in endoplasmic reticulum-associated degradation (ERAD). Here we characterize the function and regulation of USP19. We identify Hsp90 as a specific partner that binds the catalytic domain of USP19 to promote substrate association. Intriguingly, although overexpressed USP19 interacts with Derlin-1 and other ERAD machinery factors in the membrane, endogenous USP19 is mostly in the cytosol where it binds Hsp90. Accordingly, we detect neither interaction of endogenous USP19 with Derlin-1 nor significant effect on ERAD by USP19 depletion. The USP19 transmembrane domain appears to be partially stabilized in the cytosol by an interaction with its own catalytic domain, resulting in auto-inhibition of its deubiquitinating activity. These results clarify the role of USP19 in ERAD and suggest a novel DUB regulation that involves chaperone association and membrane integration. Moreover, our study indicates that the localization of tail-anchored membrane proteins can be subject to regulation in cells.

References

Jul 27, 2001·The Journal of Cell Biology·J C YoungF U Hartl
Dec 2, 2004·Biochimica Et Biophysica Acta·Cecile M Pickart, Michael J Eddins
Sep 27, 2006·The Journal of Cell Biology·Qiuyan WangYihong Ye
Apr 29, 2008·Cellular and Molecular Life Sciences : CMLS·W Li, Y Ye
Nov 13, 2008·Nature Reviews. Molecular Cell Biology·Shruthi S Vembar, Jeffrey L Brodsky
Jun 6, 2009·Annual Review of Biochemistry·Francisca E Reyes-TurcuKeith D Wilkinson
Jul 21, 2009·Cell·Mathew E SowaJ Wade Harper
Jul 25, 2009·Nature Reviews. Molecular Cell Biology·David KomanderSylvie Urbé
Oct 24, 2009·Nature Reviews. Molecular Cell Biology·Yihong Ye, Michael Rape
Aug 3, 2010·Nature·Malaiyalam MariappanRamanujan S Hegde
Aug 19, 2011·The Journal of Biological Chemistry·Yide MeiXiaolu Yang
Dec 1, 2011·The Journal of Biological Chemistry·Mikael AltunKristina Lindsten
Aug 1, 2013·Physiological Reviews·Michael J ClagueSylvie Urbé

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Citations

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Jun 29, 2016·Nature Cell Biology·Norbert VolkmarJohn C Christianson
Nov 10, 2016·International Journal of Molecular Sciences·Kumi HaradaNobuhiro Nakamura
May 10, 2017·Journal of Cell Science·Pawel Leznicki, Yogesh Kulathu
Feb 27, 2016·F1000Research·Erin S Coyne, Simon S Wing
May 28, 2019·Journal of Biomedical Science·Ming-Jer YoungJan-Jong Hung
Feb 1, 2019·Scientific Reports·Maria E GierischBeat W Schäfer
Jul 19, 2020·International Journal of Molecular Sciences·Neha SarodayaSuresh Ramakrishna
May 15, 2015·Oncotarget·Rongbin WeiShangfeng Liu
Aug 22, 2018·Cells·Anne-Claire JacominMarie-Odile Fauvarque
Feb 6, 2017·The Biochemical Journal·G Michael Preston, Jeffrey L Brodsky
Apr 2, 2021·The Journal of Cell Biology·Jacob A Culver, Malaiyalam Mariappan

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