Disease relevance of Usp4

• The oncogenic deubiquitylating enzyme (DUB) Unp/Usp4, which binds to the retinoblastoma family of tumor suppressor proteins, was originally described as a nuclear protein [1].
• We have cloned in bacteriophage a 50 kilobase region of chromosome 9 containing the Unp gene, and have determined the nucleotide sequence of the gene [2].
• Along with the previously synthesized ubiquitin-(alphaN)-valine, these synthetic proteins were used as substrates to assess the catalytic capacities of a number of diverse DUBs expressed in Escherichia coli: human HAUSP; mouse Unp; and yeast Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p [3].

High impact information on Usp4

• Further, using a Rev-green fluorescent protein-based export assay, we confirmed the existence of a nuclear export signal ((133)VEVYLLELKL(142)) in Usp4 [1].
• The murine Unp proto-oncogene encodes a nuclear ubiquitin protease whose overexpression leads to oncogenic transformation of NIH3T3 cells [4].
• We have localized the Unp gene to mouse chromosome 9 in a region of homology with human chromosome 3p [5].
• Unp, a mouse gene related to the tre oncogene [5].
• Unp cDNAs contain a large open reading frame that would encode a protein of 89 kDa [5].

Biological context of Usp4

• Identification of the mouse Usp15 gene (>69.5 kb) and human USP15 gene (145 kb) sequences in genome databases reveals that both are composed of 22 exons with identical splice sites, and both have an exon/intron structure identical to the mouse Usp4 gene, including the alternately spliced exon [6].
• The Unp proto-oncogene encodes a nuclear protein [7].
• A processed ribosomal S2 pseudogene was identified in the third intron of the Unp gene [2].

Associations of Usp4 with chemical compounds

• We found that by inhibiting nuclear export with leptomycin B, both exogenous and endogenous Usp4 accumulate in the nucleus [1].
• The murine Unp oncoprotein and its human homologue, Unph, both contain regions similar to the conserved Cys and His boxes common to all the Ubps [8].
• We have demonstrated here that the high-level expression of Unp in yeast does not disrupt the degradation of the N-end rule substrate Tyr-beta-galactosidase (betagal), the non-N-end rule substrate ubiquitin-Pro-betagal, or the degradation of abnormal, canavanine-containing proteins [8].

Other interactions of Usp4

• The murine Unp gene encodes a ubiquitin-specific protease, a member of a family of enzymes that includes the product of the human tre-2 oncogene [2].

References