TY - JOUR
T1 - UBPY
T2 - A growth-regulated human ubiquitin isopeptidase
AU - Naviglio, Silvio
AU - Matteucci, Cristian
AU - Matoskova, Brona
AU - Nagase, Takahiro
AU - Nomura, Nobuo
AU - Di Fiore, Pier Paolo
AU - Draetta, Giulio Francesco
PY - 1998/6/15
Y1 - 1998/6/15
N2 - 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.
AB - 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.
KW - Cell proliferation
KW - Growth
KW - Ubiquitin isopeptidase
KW - UBPY
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UR - http://www.scopus.com/inward/citedby.url?scp=0032526692&partnerID=8YFLogxK
U2 - 10.1093/emboj/17.12.3241
DO - 10.1093/emboj/17.12.3241
M3 - Article
C2 - 9628861
AN - SCOPUS:0032526692
VL - 17
SP - 3241
EP - 3250
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 12
ER -