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. 1998 Jun 15;17(12):3241–3250. doi: 10.1093/emboj/17.12.3241

UBPY: a growth-regulated human ubiquitin isopeptidase.

S Naviglio 1, C Mattecucci 1, B Matoskova 1, T Nagase 1, N Nomura 1, P P Di Fiore 1, G F Draetta 1
PMCID: PMC1170662  PMID: 9628861

Abstract

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.

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Selected References

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