title: Ubiquitin-specific protease 25 functions in Endoplasmic Reticulum-associated degradation.
abstract: Endoplasmic Reticulum (ER)-associated degradation (ERAD) discards abnormal proteins synthesized in the ER. Through coordinated actions of ERAD components, misfolded/anomalous proteins are recognized, ubiquitinated, extracted from the ER and ultimately delivered to the proteasome for degradation. It is not well understood how ubiquitination of ERAD substrates is regulated. Here, we present evidence that the deubiquitinating enzyme Ubiquitin-Specific Protease 25 (USP25) is involved in ERAD. Our data support a model where USP25 counteracts ubiquitination of ERAD substrates by the ubiquitin ligase HRD1, rescuing them from degradation by the proteasome.
authors.affiliation: Department of Pharmacology and Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Blount
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Burr
authors.forename: Amanda
authors.initials: A
authors.lastname: Denuc
authors.forename: Gemma
authors.initials: G
authors.lastname: Marfany
authors.forename: Sokol V
authors.initials: SV
authors.lastname: Todi
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D060746:Endoplasmic Reticulum-Associated Degradation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
chemical_list: C404488:USP25 protein, human; D057149:Ubiquitinated Proteins; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex