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PMID: 17567950 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

The role of p58IPK in protecting the stressed endoplasmic reticulum.

Molecular biology of the cell ·Vol. 18 ·No. 9 ·2007-09-00 ·Pages 3681-91

Rutkowski DT, Kang SW, Goodman AG, Garrison JL, Taunton J, Katze MG, Kaufman RJ, Hegde RS

Abstract

The preemptive quality control (pQC) pathway protects cells from acute endoplasmic reticulum (ER) stress by attenuating translocation of nascent proteins despite their targeting to translocons at the ER membrane. Here, we investigate the hypothesis that the DnaJ protein p58(IPK) plays an essential role in this process via HSP70 recruitment to the cytosolic face of translocons for extraction of translocationally attenuated nascent chains. Our analyses revealed that the heightened stress sensitivity of p58-/- cells was not due to an impairment of the pQC pathway or elevated ER substrate burden during acute stress. Instead, the lesion was in the protein processing capacity of the ER lumen, where p58(IPK) was found to normally reside in association with BiP. ER lumenal p58(IPK) could be coimmunoprecipitated with a newly synthesized secretory protein in vitro and stimulated protein maturation upon overexpression in cells. These results identify a previously unanticipated location for p58(IPK) in the ER lumen where its putative function as a cochaperone explains the stress-sensitivity phenotype of knockout cells and mice.

MeSH Terms
Amino Acid Sequence Animals Endoplasmic Reticulum/pathology Endoplasmic Reticulum Chaperone BiP HSP40 Heat-Shock Proteins/chemistry,deficiency,metabolism HeLa Cells Heat-Shock Proteins/metabolism Humans Mice Molecular Chaperones/metabolism Molecular Sequence Data NIH 3T3 Cells Prolactin/metabolism Protein Binding Protein Biosynthesis Protein Precursors/metabolism Protein Sorting Signals Protein Transport
Chemicals
Dnajc3 protein, mouse Endoplasmic Reticulum Chaperone BiP HSP40 Heat-Shock Proteins Heat-Shock Proteins Molecular Chaperones Protein Precursors Protein Sorting Signals preprolactin Prolactin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Rutkowski D Thomas
Howard Hughes Medical Institute and Departments of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0650, USA.
Kang Sang-Wook
Goodman Alan G
Garrison Jennifer L
Taunton Jack
Katze Michael G
Kaufman Randal J
Hegde Ramanujan S
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e07-03-0272
Published
2007-09-00
Epub
2007-00-13
Pages
3681-91
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1951758
Subset
IM
Grants
NIDDK NIH HHS · R01 DK-042394 · United States
Intramural NIH HHS · United States
NHLBI NIH HHS · R01 HL-052173 · United States
NIDDK NIH HHS · R01 DK042394 · United States
NHLBI NIH HHS · R01 HL052173 · United States
External Links
PubMed source DOI: 10.1091/mbc.e07-03-0272 PMC Full Text View journal details
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