PMID: 21205830

 

    Legend: Sugar

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 :
  1. 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
  2. We identified 24 ER membrane-anchored ubiquitin ligases and found Nixin / ZNRF4 to be central for the regulation of calnexin turnover
  3. 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
  4. 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