The role of p58IPK in protecting the stressed endoplasmic reticulum

D Thomas Rutkowski; Sang-Wook Kang; Alan G Goodman; Jennifer L Garrison; Jack Taunton; Michael G Katze; Randal J Kaufman; Ramanujan S Hegde

doi:10.1091/mbc.E07-03-0272

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The role of p58IPK in protecting the stressed endoplasmic reticulum

Journal article

Open access

Peer reviewed

The role of p58IPK in protecting the stressed endoplasmic reticulum

D Thomas Rutkowski, Sang-Wook Kang, Alan G Goodman, Jennifer L Garrison, Jack Taunton, Michael G Katze, Randal J Kaufman and Ramanujan S Hegde

Molecular biology of the cell, Vol.18(9), pp.3681-3691

09/2007

DOI: 10.1091/mbc.E07-03-0272

PMCID: PMC1951758

PMID: 17567950

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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.

Amino Acid Sequence

NIH 3T3 Cells

HSP40 Heat-Shock Proteins - metabolism

Protein Biosynthesis

Molecular Chaperones - metabolism

Heat-Shock Proteins - metabolism

Humans

Molecular Sequence Data

HSP40 Heat-Shock Proteins - deficiency

Protein Sorting Signals

Protein Precursors - metabolism

Protein Transport

Prolactin - metabolism

Endoplasmic Reticulum - pathology

Animals

Protein Binding

Mice

HeLa Cells

HSP40 Heat-Shock Proteins - chemistry

Details

Title: Subtitle: The role of p58IPK in protecting the stressed endoplasmic reticulum
Creators: D Thomas Rutkowski - Howard Hughes Medical Institute and Departments of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0650, USA
Sang-Wook Kang - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Alan G Goodman
Jennifer L Garrison
Jack Taunton
Michael G Katze
Randal J Kaufman
Ramanujan S Hegde
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.18(9), pp.3681-3691
DOI: 10.1091/mbc.E07-03-0272
PMID: 17567950
PMCID: PMC1951758
NLM abbreviation: Mol Biol Cell
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: R01 HL-052173 / NHLBI NIH HHS Intramural NIH HHS R01 DK042394 / NIDDK NIH HHS R01 HL052173 / NHLBI NIH HHS R01 DK-042394 / NIDDK NIH HHS
Language: English
Date published: 09/2007
Academic Unit: Anatomy and Cell Biology; Internal Medicine
Record Identifier: 9984094505002771

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