title: Defining human ERAD networks through an integrative mapping strategy.
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.
authors: Department of Biology & Bio-X Program, Stanford University, Stanford, California 94305, USA.
authors: John C
authors: JC
authors: Christianson
authors: James A
authors: JA
authors: Olzmann
authors: Thomas A
authors: TA
authors: Shaler
authors: Mathew E
authors: ME
authors: Sowa
authors: Eric J
authors: EJ
authors: Bennett
authors: Caleb M
authors: CM
authors: Richter
authors: Ryan E
authors: RE
authors: Tyler
authors: Ethan J
authors: EJ
authors: Greenblatt
authors: J Wade
authors: JW
authors: Harper
authors: Ron R
authors: RR
authors: Kopito
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D059748:Proteolysis; D034622:RNA Interference; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D011506:Proteins; C117384:SEL1L protein, human; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease