title: Recent technical developments in the study of ER-associated degradation.
abstract: Endoplasmic reticulum-associated degradation (ERAD) is a mechanism during which native and misfolded proteins are recognized and retrotranslocated across the ER membrane to the cytosol for degradation by the ubiquitin-proteasome system. Like other cellular pathways, the factors required for ERAD have been analyzed using both conventional genetic and biochemical approaches. More recently, however, an integrated top-down approach has identified a functional network that underlies the ERAD system. In turn, bottom-up reconstitution has become increasingly sophisticated and elucidated the molecular mechanisms underlying substrate recognition, ubiquitylation, retrotranslocation, and degradation. In addition, a live cell imaging technique and a site-specific in vivo photo-crosslinking approach have further dissected specific steps during ERAD. These technical developments have revealed an unexpected dynamicity of the membrane-associated ERAD complex. In this article, we will discuss how these technical developments have improved our understanding of the ERAD pathway and have led to new questions.
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan. Electronic address: z47875a@cc.nagoya-u.ac.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakatsukasa
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kamura
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: jbrodsky@pitt.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D011506:Proteins; D046988:Proteasome Endopeptidase Complex