Defining human ERAD networks through an integrative mapping strategy

JC Christianson, JA Olzmann, TA Shaler, ME Sowa… - Nature cell …, 2012 - nature.com
JC Christianson, JA Olzmann, TA Shaler, ME Sowa, EJ Bennett, CM Richter, RE Tyler…
Nature cell biology, 2012nature.com
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 …
Abstract
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.
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