The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD

The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD

Bibliographic Details
Main Author: Jameel, Amer
Language:English
Published: University of Cincinnati / OhioLINK 2010
Subjects:
Cellular Biology
surfactant protein c
heat shock protein
Grp170
BiP
Nucleotide Exchange Factor
ERAD
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1276974476
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin12769744762021-08-03T06:14:05Z The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD Jameel, Amer Cellular Biology surfactant protein c heat shock protein Grp170 BiP Nucleotide Exchange Factor ERAD Interstitial lung disease (ILD) encompasses a wide range of disorders that impairs gas exchange through thickening of the lung interstitium in children and adults. Mutations in the gene SFTPC encoding surfactant protein C (SP-C) are associated with development of ILD in children and adults. The mutations can result in misfolding of mutant SP-C with the potential to form cytotoxic aggregates. Thus to prevent aggregation, mutant SP-C is directed to the endoplasmic reticulum-associated degradation (ERAD) pathway for rapid removal from the ER and degradation by the proteasome in the cytosol. Glycoprotein ERAD is well characterized, however SP-C is non-glycosylated and cleared by the poorly characterized non-glycosylated ERAD pathway. Binding immunoglobulin protein (BiP), ERdj4 and ERdj5 were discovered to function as chaperones for ERAD of mutant SP-C. BiP ATPase activity is suggested to play a central role in ERAD of mutant SP-C. J-domain proteins ERdj4 and ERdj5 direct binding of BiP to misfolded substrate by enhancing BiP ATPase activity. Only regeneration of ATP bound BiP will execute release of misfolded substrate for dislocation and degradation; this essential step requires a nucleotide exchange factor (NEF). We hypothesize that the NEF Grp170 best serves mutant SP-C ERAD through localization to non-glycosylated ERAD components by the substrate binding domain (SBD) and mediating BiP release through the Grp170 nucleotide binding domain (NBD). 2010-08-05 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1276974476 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1276974476 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Cellular Biology
surfactant protein c
heat shock protein
Grp170
BiP
Nucleotide Exchange Factor
ERAD
spellingShingle Cellular Biology
surfactant protein c
heat shock protein
Grp170
BiP
Nucleotide Exchange Factor
ERAD
Jameel, Amer
The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
author Jameel, Amer
author_facet Jameel, Amer
author_sort Jameel, Amer
title The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
title_short The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
title_full The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
title_fullStr The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
title_full_unstemmed The Role of Grp170 in SP-C<sup>Δexon4</sup> ERAD
title_sort role of grp170 in sp-c<sup>δexon4</sup> erad
publisher University of Cincinnati / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1276974476
work_keys_str_mv AT jameelamer theroleofgrp170inspcsupdexon4superad
AT jameelamer roleofgrp170inspcsupdexon4superad
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