PMID- 17699585
OWN - NLM
STAT- MEDLINE
DCOM- 20080125
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Linking)
VI  - 18
IP  - 11
DP  - 2007 Nov
TI  - Regulation of ubiquitin-proteasome system mediated degradation by cytosolic 
      stress.
PG  - 4279-91
AB  - ER-associated, ubiquitin-proteasome system (UPS)-mediated degradation of the 
      wild-type (WT) gap junction protein connexin32 (Cx32) is inhibited by mild forms 
      of cytosolic stress at a step before its dislocation into the cytosol. We show 
      that the same conditions (a 30-min, 42 degrees C heat shock or oxidative stress 
      induced by arsenite) also reduce the endoplasmic reticulum (ER)-associated 
      turnover of disease-causing mutants of Cx32 and the cystic fibrosis transmembrane 
      conductance regulator (CFTR), as well as that of WT CFTR and unassembled Ig light 
      chain. Stress-stabilized WT Cx32 and CFTR, but not the mutant/unassembled 
      proteins examined, could traverse the secretory pathway. Heat shock also slowed 
      the otherwise rapid UPS-mediated turnover of the cytosolic proteins myoD and 
      GFPu, but not the degradation of an ubiquitination-independent construct 
      (GFP-ODC) closely related to the latter. Analysis of mutant Cx32 from cells 
      exposed to proteasome inhibitors and/or cytosolic stress indicated that stress 
      reduces degradation at the level of substrate polyubiquitination. These findings 
      reveal a new link between the cytosolic stress-induced heat shock response, 
      ER-associated degradation, and polyubiquitination. Stress-denatured proteins may 
      titer a limiting component of the ubiquitination machinery away from pre-existing 
      UPS substrates, thereby sparing the latter from degradation.
FAU - Kelly, Sean M
AU  - Kelly SM
AD  - Department of Biochemistry and Molecular Biology, Oregon Health & Science 
      University, Portland, OR 97239, USA.
FAU - Vanslyke, Judy K
AU  - Vanslyke JK
FAU - Musil, Linda S
AU  - Musil LS
LA  - eng
GR  - R01 NS040740/NS/NINDS NIH HHS/United States
GR  - T32 EY007123/EY/NEI NIH HHS/United States
GR  - R01 NS40740-01/NS/NINDS NIH HHS/United States
GR  - T32-EY07123-16/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070815
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Connexins)
RN  - 0 (Ubiquitin)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Connexins/genetics/metabolism
MH  - Cricetinae
MH  - Cricetulus
MH  - Cytosol/*metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Glutamic Acid/genetics/metabolism
MH  - Hot Temperature
MH  - Mutation/genetics
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Transport
MH  - Substrate Specificity
MH  - Ubiquitin/*metabolism
PMC - PMC2043544
EDAT- 2007/08/19 09:00
MHDA- 2008/01/26 09:00
PMCR- 2007/12/25
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/01/26 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
PHST- 2007/12/25 00:00 [pmc-release]
AID - E07-05-0487 [pii]
AID - 3265750 [pii]
AID - 10.1091/mbc.e07-05-0487 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2007 Nov;18(11):4279-91. doi: 10.1091/mbc.e07-05-0487. Epub 2007 
      Aug 15.