Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cell Biol. 2012 Aug 6;198(3):371-85. doi: 10.1083/jcb.201202005.

ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load.

Author information

1
Metabolic Research Laboratories, University of Cambridge, Cambridge CB2 0QQ, England, UK. jec202@cam.ac.uk

Erratum in

  • J Cell Biol. 2014 Nov 24;207(4):569.

Abstract

Gene expression programs that regulate the abundance of the chaperone BiP adapt the endoplasmic reticulum (ER) to unfolded protein load. However, such programs are slow compared with physiological fluctuations in secreted protein synthesis. While searching for mechanisms that fill this temporal gap in coping with ER stress, we found elevated levels of adenosine diphosphate (ADP)-ribosylated BiP in the inactive pancreas of fasted mice and a rapid decline in this modification in the active fed state. ADP ribosylation mapped to Arg470 and Arg492 in the substrate-binding domain of hamster BiP. Mutations that mimic the negative charge of ADP-ribose destabilized substrate binding and interfered with interdomain allosteric coupling, marking ADP ribosylation as a rapid posttranslational mechanism for reversible inactivation of BiP. A kinetic model showed that buffering fluctuations in unfolded protein load with a recruitable pool of inactive chaperone is an efficient strategy to minimize both aggregation and costly degradation of unfolded proteins.

Comment in

PMID:
22869598
PMCID:
PMC3413365
DOI:
10.1083/jcb.201202005
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center