First Author | Zhu Y | Year | 1996 |
Journal | Proc Natl Acad Sci U S A | Volume | 93 |
Issue | 8 | Pages | 3275-9 |
PubMed ID | 8622927 | Mgi Jnum | J:35111 |
Mgi Id | MGI:82565 | Doi | 10.1073/pnas.93.8.3275 |
Citation | Zhu Y, et al. (1996) DUB-1, a deubiquitinating enzyme with growth-suppressing activity. Proc Natl Acad Sci U S A 93(8):3275-9 |
abstractText | 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). |