UBPY: a growth-regulated human ubiquitin isopeptidase.
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.
Naviglio
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S
European Institute of Oncology, Milan, Italy.
Mattecucci
C
C
Matoskova
B
B
Nagase
T
T
Nomura
N
N
Di Fiore
P P
PP
Draetta
G F
GF
D000818:Animals; D019759:Carbon-Nitrogen Lyases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D010450:Endopeptidases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D014162:Transfection; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; D011994:Recombinant Proteins; D014452:Ubiquitins; D010450:Endopeptidases; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase; C541536:Usp8 protein, mouse; C091939:ubiquitin isopeptidase; D019759:Carbon-Nitrogen Lyases; C034300:isopeptidase