Premium
UBPY: a growth‐regulated human ubiquitin isopeptidase
Author(s) -
Naviglio Silvio,
Matteucci Cristian,
Matoskova Brona,
Nagase Takahiro,
Nomura Nobuo,
Di Fiore Pier Paolo,
Draetta Giulio Francesco
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.12.3241
Subject(s) - biology , ubiquitin , microbiology and biotechnology , cell growth , immunoprecipitation , proteasome , f box protein , deubiquitinating enzyme , cell , ubiquitin ligase , cell culture , biochemistry , gene , genetics
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.