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http://purl.uniprot.org/citations/21743475http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21743475http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21743475http://www.w3.org/2000/01/rdf-schema#comment"A substantial proportion of the genome encodes membrane proteins that are delivered to the endoplasmic reticulum by dedicated targeting pathways. Membrane proteins that fail targeting must be rapidly degraded to avoid aggregation and disruption of cytosolic protein homeostasis. The mechanisms of mislocalized protein (MLP) degradation are unknown. Here we reconstitute MLP degradation in vitro to identify factors involved in this pathway. We find that nascent membrane proteins tethered to ribosomes are not substrates for ubiquitination unless they are released into the cytosol. Their inappropriate release results in capture by the Bag6 complex, a recently identified ribosome-associating chaperone. Bag6-complex-mediated capture depends on the presence of unprocessed or non-inserted hydrophobic domains that distinguish MLPs from potential cytosolic proteins. A subset of these Bag6 complex 'clients' are transferred to TRC40 for insertion into the membrane, whereas the remainder are rapidly ubiquitinated. Depletion of the Bag6 complex selectively impairs the efficient ubiquitination of MLPs. Thus, by its presence on ribosomes that are synthesizing nascent membrane proteins, the Bag6 complex links targeting and ubiquitination pathways. We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.org/dc/terms/identifier"doi:10.1038/nature10181"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.org/dc/terms/identifier"doi:10.1038/nature10181"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Sharma A."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Sharma A."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Hegde R.S."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Hegde R.S."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Eshleman H.D."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Eshleman H.D."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Gutierrez E."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Gutierrez E."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Hessa T."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Hessa T."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Mariappan M."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/author"Mariappan M."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/name"Nature"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/name"Nature"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/pages"394-397"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/pages"394-397"xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/title"Protein targeting and degradation are coupled for elimination of mislocalized proteins."xsd:string
http://purl.uniprot.org/citations/21743475http://purl.uniprot.org/core/title"Protein targeting and degradation are coupled for elimination of mislocalized proteins."xsd:string