. "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." . . "Nat. Cell Biol." . "Harper J.W." . "Kopito R.R." . "Sowa M.E." . "Bennett E.J." . "Christianson J.C." . "Richter C.M." . "Olzmann J.A." . "Shaler T.A." . "Tyler R.E." . "Greenblatt E.J." . "2012"^^ . "93-105" . "Defining human ERAD networks through an integrative mapping strategy." . "14" . "doi:10.1038/ncb2383" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .