<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Ferris, Sean P.</dc:creator>
  <dc:creator>Jaber, Nikita S.</dc:creator>
  <dc:creator>Molinari, Maurizio</dc:creator>
  <dc:creator>Arvan, Peter</dc:creator>
  <dc:creator>Kaufman, Randal J.</dc:creator>
  <dc:date>2013-06-28</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Protein folding in the endoplasmic reticulum (ER) is error prone, and ER quality control (ERQC) processes ensure that only correctly folded proteins are exported from  the ER. Glycoproteins can be retained in the ER by ERQC, and this retention contributes to multiple human diseases, termed ER storage diseases. UDP- glucose:glycoprotein glucosyltransferase (UGGT1) acts as a central component of glycoprotein ERQC, monoglucosylating deglucosylated N-glycans of incompletely  folded glycoproteins and promoting subsequent reassociation with the lectin-like chaperones calreticulin and calnexin. The extent to which UGGT1 influences  glycoprotein folding, however, has only been investigated for a few selected substrates. Using mouse embryonic fibroblasts lacking UGGT1 or those with UGGT1  complementation, we investigated the effect of monoglucosylation on the soluble/insoluble distribution of two misfolded α1-antitrypsin (AAT) variants responsible for  AAT deficiency disease: null Hong Kong (NHK) and Z allele. Whereas substrate solubility increases directly with the number of N-linked glycosylation sites, our results  indicate that additional solubility is conferred by UGGT1 enzymatic activity. Monoglucosylation-dependent solubility decreases both BiP association with NHK and  unfolded protein response activation, and the solubility increase is blocked in cells deficient for calreticulin. These results suggest that UGGT1-dependent  monoglucosylation of N-linked glycoproteins promotes substrate solubility in the ER.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://n2t.net/ark:/12658/srd1318936</dc:identifier>
  <dc:identifier>https://susi.usi.ch/global/documents/318936</dc:identifier>
  <dc:identifier>https://susi.usi.ch/documents/318936/files/Ferris_MBC_2013.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/ark/12658/srd1318936</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>CC BY-NC-SA</dc:rights>
  <dc:source>Molecular biology of the cell. - 2013, vol. 24, no. 17, p. 2597-2608</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">UDP-glucose : glycoprotein glucosyltransferase (UGGT1) promotes substrate solubility in the endoplasmic reticulum</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>