UBPY: A growth-regulated human ubiquitin isopeptidase

Silvio Naviglio, Cristian Matteucci, Brona Matoskova, Takahiro Nagase, Nobuo Nomura, Pier Paolo Di Fiore, Giulio Francesco Draetta

Research output: Contribution to journalArticlepeer-review


The ubiquitin pathway has been implicated in the regulation of the abundance of proteins that control cell growth and proliferation. We have identified and characterized a novel human ubiquitin isopeptidase, UBPY, which both as a recombinant protein and upon immunoprecipitation from cell extracts is able to cleave linear or isopeptide-linked ubiquitin chains. UBPY accumulates upon growth stimulation of starved human fibroblasts, and its levels decrease in response to growth arrest induced by cell-cell contact. Inhibition of UBPY accumulation by antisense plasmid microinjection prevents fibroblasts from entering S-phase in response to serum stimulation. By increasing or decreasing the cellular abundance of UBPY or by overexpressing a catalytic site mutant, we detect substantial changes in the total pattern of protein ubiquitination, which correlate stringently with cell proliferation. Our results suggest that UBPY plays a role in regulating the overall function of the ubiquitin-proteasome pathway. Affecting the function of a specific UBP in vivo could provide novel tools for controlling mammalian cell proliferation.

Original languageEnglish
Pages (from-to)3241-3250
Number of pages10
JournalEMBO Journal
Issue number12
Publication statusPublished - Jun 15 1998


  • Cell proliferation
  • Growth
  • Ubiquitin isopeptidase
  • UBPY

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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