Cloning and characterization of Unp: A novel nuclear proto-oncogene.
|Title:||Cloning and characterization of Unp: A novel nuclear proto-oncogene.|
|Abstract:||The cloning and characterization of a novel gene, Unp (for Ubiquitin-specific Nuclear Protease), is described in this thesis. This gene was identified during a survey for candidate genes for the retroviral insertional mutation Mpv 20. Unp is transcribed into two ubiquitously expressed mRNAs of approximately 3.5 and 3.7 kb. The two mRNAs vary at their $3\prime$ ends due to alternative usage of two degenerate polyadenylation signals. The $5\prime$ UTR of Unp contains several minicistrons, which suggest a growth related function for this gene. The Unp gene has been mapped to mouse chromosome 9 and human chromosome 3 in a region which is implicated in several types of human cancers based on loss of heterozygocity. This suggests a possible tumor suppressor function for this gene. The predicted amino acid sequence of the Unp protein contains several conserved motifs, including p53 type nuclear localization signal, consensus for binding to the retinoblastoma protein, and the Cys and His domains conserved in yeast ubiquitin proteases. The pRb binding consensus is present in the region of Unp which shares homology to the recombinant human oncogene tre-2. Unp protein is localized in the nucleus and migrates at a higher molecular mass than expected, suggesting that this protein is post-translationally modified. Unp is tumorigenic in athymic mice showing that it is a proto-oncogene. The protein product of Unp is a ubiquitin-specific protease. The Unp gene is highly polymorphic in humans, and loss of Unp sequences is detected in 1 out of the 7 informative human lung tumors analyzed.|
|Collection||Thèses, 1910 - 2010 // Theses, 1910 - 2010|