title: Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity.
abstract: UnpEL (also known as Usp4 or Unph) is an oncogenic protein, because its expression with a strong promoter results in the tumorigenic transformation of NIH3T3 cells injected into nude mice. Although the structure of UnpEL is that of a deubiquitinating enzyme, neither its precise function in mammalian cells nor the mechanism of UnpEL-mediated tumorigenesis is known. Here, we show that UnpEL functions as a deubiquitinating enzyme in human HEK293T cells and its isopeptidase activity deconjugates ubiquitin specifically from a UnpEL-interacting protein Ro52. We further show that UnpEL translocates to the cytoplasmic rod-like structures and colocalizes with Ro52 when Ro52 is overexpressed in HEK293 cells. These results suggest that UnpEL colocalizes with the unubiquitinated form of Ro52 to the cytoplasmic rod-like structures, where it keeps Ro52 unubiquitinated. The continuous deubiquitination of Ro52 might be involved in tumorigenesis.
authors.affiliation: Department of Cardiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
mesh_terms: D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D000099207:SS-A Antigen
chemical_list: D010450:Endopeptidases; D007527:Isoenzymes; D015513:Oncogene Proteins; D010447:Peptide Hydrolases; D012261:Ribonucleoproteins; D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D000099207:SS-A Antigen; C486203:USP4 protein, human; C438343:UnpEL enzyme