DUB-1, a deubiquitinating enzyme with growth-suppressing activity.
Y Zhu, M Carroll, FR Papa… - Proceedings of the …, 1996 - National Acad Sciences
Y Zhu, M Carroll, FR Papa, M Hochstrasser, AD D'Andrea
Proceedings of the National Academy of Sciences, 1996•National Acad SciencesCytokines regulate cell growth by inducing the expression of specific target genes. Using the
differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-
1 (for deubiquitinating enzyme). DUB-1 is related to members of the UBP superfamily of
deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-
transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase
protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol …
differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-
1 (for deubiquitinating enzyme). DUB-1 is related to members of the UBP superfamily of
deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-
transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase
protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol …
Cytokines regulate cell growth by inducing the expression of specific target genes. Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-1 (for deubiquitinating enzyme). DUB-1 is related to members of the UBP superfamily of deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. Continuous expression of DUB-1 from a steroid-inducible promoter induced growth arrest in the G1 phase of the cell cycle. Cells arrested by DUB-1 expression remained viable and resumed proliferation upon steroid withdrawal. Our results suggest that DUB-1 regulates cellular growth by modulating either the ubiquitin-dependent proteolysis or the ubiquitination state of an unknown growth regulatory factor(s).
National Acad Sciences