Title : A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger
proteins identifies
Nixin /
ZNRF4 as a regulator of
calnexin stability and ER homeostasis
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
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):