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Defining human ERAD networks through an integrative mapping strategy.

Proteins that fail to correctly fold or assemble into oligomeric complexes in the endoplasmic reticulum (ER) are degraded by a ubiquitin- and proteasome-dependent process known as ER-associated degradation (ERAD). Although many individual components of the ERAD system have been identified, how these proteins are organized into a functional network that coordinates recognition, ubiquitylation and dislocation of substrates across the ER membrane is not well understood. We have investigated the functional organization of the mammalian ERAD system using a systems-level strategy that integrates proteomics, functional genomics and the transcriptional response to ER stress. This analysis supports an adaptive organization for the mammalian ERAD machinery and reveals a number of metazoan-specific genes not previously linked to ERAD.

Pubmed ID: 22119785

Authors

  • Christianson JC
  • Olzmann JA
  • Shaler TA
  • Sowa ME
  • Bennett EJ
  • Richter CM
  • Tyler RE
  • Greenblatt EJ
  • Harper JW
  • Kopito RR

Journal

Nature cell biology

Publication Data

January 23, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: F32 GM086026
  • Agency: NIGMS NIH HHS, Id: F32 GM086026-01
  • Agency: NIGMS NIH HHS, Id: F32 GM086026-02
  • Agency: NIGMS NIH HHS, Id: F32 GM086026-03
  • Agency: NIA NIH HHS, Id: R01 AG011085
  • Agency: NIGMS NIH HHS, Id: R01 GM054137
  • Agency: NIGMS NIH HHS, Id: R01 GM070565
  • Agency: NIGMS NIH HHS, Id: R01 GM074874
  • Agency: NIGMS NIH HHS, Id: R01 GM074874-06
  • Agency: NINDS NIH HHS, Id: R01 NS042842
  • Agency: NINDS NIH HHS, Id: R01 NS042842-09

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Endoplasmic Reticulum
  • Endoplasmic Reticulum-Associated Degradation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex
  • Protein Folding
  • Proteins
  • Proteolysis
  • RNA Interference
  • Receptors, Autocrine Motility Factor
  • Ubiquitin-Protein Ligases