title: Ubiquitin-specific protease 7 is a regulator of ubiquitin-conjugating enzyme UbE2E1.
abstract: Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme found in all eukaryotes that catalyzes the removal of ubiquitin from specific target proteins. Here, we report that UbE2E1, an E2 ubiquitin conjugation enzyme with a unique N-terminal extension, is a novel USP7-interacting protein. USP7 forms a complex with UbE2E1 in vitro and in vivo through the ASTS USP7 binding motif within its N-terminal extension in an identical manner with other known USP7 binding proteins. We show that USP7 attenuates UbE2E1-mediated ubiquitination, an effect that requires the N-terminal ASTS sequence of UbE2E1 as well as the catalytic activity of USP7. Additionally, USP7 is critical in maintaining the steady state levels of UbE2E1 in cells. This study reveals a new cellular mechanism that couples the opposing activities of the ubiquitination machinery and a deubiquitinating enzyme to maintain and modulate the dynamic balance of the ubiquitin-proteasome system.
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Feroz
authors.initials: F
authors.lastname: Sarkari
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Keith
authors.initials: K
authors.lastname: Wheaton
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Anthony
authors.initials: A
authors.lastname: La Delfa
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Majda
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Faryal
authors.initials: F
authors.lastname: Shaikh
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3.
authors.forename: Rahima
authors.initials: R
authors.lastname: Khatun
authors.affiliation: Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 1L7.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Frappier
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3. Electronic address: vsaridak@yorku.ca.
authors.forename: Vivian
authors.initials: V
authors.lastname: Saridakis
authors.affiliation: Department of Biology, York University, Toronto, Ontario M3J 1P3. Electronic address: yisheng@yorku.ca.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sheng
mesh_terms: D020816:Amino Acid Motifs; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination / Q000502:physiology*
chemical_list: C489963:UBE2E1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D046988:Proteasome Endopeptidase Complex
keywords: Deubiquitination; E3 Ubiquitin Ligase; Protein Structure; Ubiquitin-conjugating Enzyme (Ubc); Ubiquitination