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A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis

Neutzner, A. and Neutzner, M. and Benischke, A. S. and Ryu, S. W. and Frank, S. and Youle, R. J. and Karbowski, M.. (2011) A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis. Journal of biological chemistry, Vol. 286, H. 10. pp. 8633-8643.

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Official URL: http://edoc.unibas.ch/dok/A6005399

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Abstract

To identify novel regulators of endoplasmic reticulum (ER)-linked protein degradation and ER function, we determined the entire inventory of membrane-spanning RING finger E3 ubiquitin ligases localized to the ER. We identified 24 ER membrane-anchored ubiquitin ligases and found Nixin/ZNRF4 to be central for the regulation of calnexin turnover. Ectopic expression of wild type Nixin induced a dramatic down-regulation of the ER-localized chaperone calnexin that was prevented by inactivation of the Nixin RING domain. Importantly, Nixin physically interacts with calnexin in a glycosylation-independent manner, induces calnexin ubiquitination, and p97-dependent degradation, indicating an ER-associated degradation-like mechanism of calnexin turnover.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Neuro- und Muskelpathologie (Frank)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Ocular Pharmacology and Physiology (Neutzner/Meyer)
UniBasel Contributors:Frank, Stephan and Neutzner, Albert
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Biological Chemists
ISSN:0021-9258
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:25 Oct 2013 08:32

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