title: Regulation of USP28 deubiquitinating activity by SUMO conjugation.
abstract: USP28 (ubiquitin-specific protease 28) is a deubiquitinating enzyme that has been implicated in the DNA damage response, the regulation of Myc signaling, and cancer progression. The half-life stability of major regulators of critical cellular pathways depends on the activities of specific ubiquitin E3 ligases that target them for proteosomal degradation and deubiquitinating enzymes that promote their stabilization. One function of the post-translational small ubiquitin modifier (SUMO) is the regulation of enzymatic activity of protein targets. In this work, we demonstrate that the SUMO modification of the N-terminal domain of USP28 negatively regulates its deubiquitinating activity, revealing a role for the N-terminal region as a regulatory module in the control of USP28 activity. Despite the presence of ubiquitin-binding domains in the N-terminal domain, its truncation does not impair deubiquitinating activity on diubiquitin or polyubiquitin chain substrates. In contrast to other characterized USP deubiquitinases, our results indicate that USP28 has a chain preference activity for Lys(11), Lys(48), and Lys(63) diubiquitin linkages.
authors.affiliation: From the Institut de Biotecnologia i de Biomedicina and Departament de Bioquimica i Biologia Molecular, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: the Institute for Research in Biomedicine, 08028 Barcelona, Spain.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Knobel
authors.affiliation: the Institute for Research in Biomedicine, 08028 Barcelona, Spain.
authors.forename: Travis H
authors.initials: TH
authors.lastname: Stracker
authors.affiliation: From the Institut de Biotecnologia i de Biomedicina and Departament de Bioquimica i Biologia Molecular, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain and david.reverter@uab.cat.
authors.forename: David
authors.initials: D
authors.lastname: Reverter
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000378:metabolism*; D013379:Substrate Specificity; D058207:Sumoylation; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; C442902:USP28 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Proteolytic Enzyme; SUMO-interacting Motif (SIM); Sumoylation; Ubiquitin; Ubiquitin-dependent Protease