High impact information on Dub1

• A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response [1].
• The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene [2].
• The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells [3].
• The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene [4].
• Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-1 (for deubiquitinating enzyme) [5].

Biological context of Dub1

• In vivo and in vitro deubiquitinating enzyme assays showed that DUB-1A has functional deubiquitinating activity and that the 5'-flanking sequence of Dub-1A has a functional enhancer domain as shown in Dub-1 and Dub-2A [6].
• Recently, we isolated the Dub-2A gene, which encodes a novel murine deubiquitinating enzyme subfamily member, from a bacterial artificial chromosome library clone by PCR amplification with degenerate PCR primers for the Dub-2 cDNA (Baek, K.-H., Mondoux, M. A., Jaster, R., Fire-Levin E., and D'Andrea, A. D. (2001) Blood 98, 636-642) [6].
• To investigate the function of deubiquitinating enzymes on ischemia-induced neural cell apoptosis in vivo, we analyzed gracile axonal dystrophy (gad) mice with an exon deletion for ubiquitin carboxy terminal hydrolase-L1 (UCH-L1), a neuron-specific deubiquitinating enzyme [7].
• In this study, we searched for Hbp-binding proteins by a far Western screening and isolated a mouse cDNA clone encoding a deubiquitinating enzyme mUBPY as an Hbp SH3-binding protein. mUBPY has two Hbp-SH3 domain binding sites [8].
• Sequence analysis revealed a fusion product of the p85beta subunit of phosphatidylinositol (PI) 3-kinase and HUMORF8, a putative deubiquitinating enzyme, which has been generated during the DNA transfection process [9].

Anatomical context of Dub1

• DUB-1A, a novel deubiquitinating enzyme subfamily member, is polyubiquitinated and cytokine-inducible in B-lymphocytes [6].
• The mouse USP8/mUBPy gene codifies a deubiquitinating enzyme expressed preferentially in testis and brain [10].
• The deubiquitinating enzyme mUBPy interacts with the sperm-specific molecular chaperone MSJ-1: the relation with the proteasome, acrosome, and centrosome in mouse male germ cells [10].
• We have previously found that the deubiquitinating enzyme Fam is colocalized with AF-6, one of the effectors of the Ras small GTPase, at cell-cell contact sites in epithelial cells and interacts with AF-6 in vivo and in vitro [11].
• Recently, another deubiquitinating enzyme gene DUB-2A, expressed also in T-lymphocytes, has been isolated and we, in this study, found that Dub-2A has isopeptidase activity and there are at least 4 conserved amino acids (Cys60, Asp133, His298, and His307) that are required for catalytic activity of the enzyme [12].

Associations of Dub1 with chemical compounds

• The deubiquitinating enzyme UCH-L3 is labeled by both ubiquitin vinyl sulfone and Nedd8 vinyl sulfone [13].
• We show that the deubiquitinating enzyme USP7 (HAUSP) is proteolytically processed upon dexamethasone-, gamma-irradiation-, and antigen-induced cell death [14].
• Phosphorylation of the deubiquitinating enzyme USP8 at serine 680 was found essential for its interaction with 14-3-3epsilon and for maintaining USP8 in the cytosol [15].

Other interactions of Dub1

• HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized [16].
• mUBPy and MSJ-1, a deubiquitinating enzyme and a molecular chaperone specifically expressed in testis, associate with the acrosome and centrosome in mouse germ cells [17].
• Mass spectrometry analysis identified this substrate as FLJ20113, an open reading frame that corresponds to otubain 1, a deubiquitinating enzyme implicated in immune cell clonal anergy [18].
• Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69 [19].
• The ubiquitin-proteasome pathway in thymocyte apoptosis: caspase-dependent processing of the deubiquitinating enzyme USP7 (HAUSP) [14].

Analytical, diagnostic and therapeutic context of Dub1

• Molecular cloning of rHAUSP encoding a deubiquitinating enzyme in rat testis [20].
• We have identified a full-length mouse UBH1 cDNA, encoding a putative deubiquitinating enzyme, from the testis by RT-PCR using primers prepared from sequences conserved amongst deubiquitinating enzymes [21].

References