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Calnexin levels are regulated by the ER localized ubiquitin ligase Nixin
Author(s) -
Neutzner Albert,
Neutzner Melanie,
Benischke AnneSophie,
Ryu SeungWook,
Youle Richard J,
Karbowski Mariusz
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.910.1
Subject(s) - calnexin , ubiquitin ligase , microbiology and biotechnology , endoplasmic reticulum , ubiquitin , chaperone (clinical) , endoplasmic reticulum associated protein degradation , unfolded protein response , proteasome , chemistry , ring finger , membrane protein , biology , biochemistry , membrane , calreticulin , medicine , pathology , gene
To identify novel regulators of ER linked protein degradation and ER function, we determined the entire inventory of membrane spanning RING finger proteins localized to the ER. We identified twenty four ER membrane anchored ubiquitin ligases and found Nixin to be central for the regulation of calnexin turnover. Using fluorescence protease protection and hydrophobicity plotting, we established that Nixin spans the ER membrane once, thus exposing its RING domain to the cytosol. Ectopic expression of wild type Nixin induced a strong downregulation of the ER localized chaperone calnexin that was prevented by inactivation of the Nixin RING domain as well as by proteasomal inhibition. Furthermore, Nixin physically interacts with calnexin in a glycosylation independent manner and enhances calnexin ubiquitination. Taken together, the ER membrane‐anchored ubiquitin ligase Nixin regulates calnexin levels through proteasomal degradation and thus might play a role during ER stress recovery when calnexin levels are adjusted to pre‐stress levels.