Defining human ERAD networks through an integrative mapping strategy.

Journal article

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.

Authors: Christianson, J; Olzmann, J; Shaler, T; Sowa, M; Bennett, E

• Publication status: Published
• Journal: Nature cell biology
• Volume: 14
• Issue: 1
• Pages: 93-105
• Publication date: 2012-01-01
• DOI: 10.1038/ncb2383
• EISSN: 1476-4679
• ISSN: 1465-7392
• Language: English
• Keywords: Hela Cells; Proteasome Endopeptidase Complex; Receptors, Autocrine Motility Factor; HEK293 Cells; Proteins; Animals; Endoplasmic Reticulum; RNA Interference; Proteolysis; Molecular Sequence Data; Ubiquitin-Protein Ligases; Humans; Endoplasmic Reticulum-Associated Degradation; Protein Folding; Amino Acid Sequence