Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression.

Abstract

Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH), which codes for a 282 amino acids putative zinc finger protein. HUMSIAH is localized on human chromosome 16ql2-ql3. This gene is activated during the physiological program of cell death in the intestinal epithelium. Moreover, human cancer-derived cells selected for suppression of their tumorigenic phenotype exhibit constitutively elevated levels of HUMSIAH mRNA. A similar pattern of expression is also displayed by the p2lwan. These results suggest that mammalian seven in absentia gene, which is a target for activation by p53, may play a role in apoptosis and tumor suppression.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…While induction of the p21 WAF1 gene has been shown not to be essential for p53-mediated apoptosis, p53 induces the expression of Fas/APO1 (Owen-Schaub et al, 1995), member of the death receptor family, BAX Selvakumaran et al, 1994;Miyashita and Reed, 1995;Han et al, 1996) the product of which can antagonize the anti-apoptotic activity of Bcl-2 (White, 1996) and IGF-BP3 (Buckbinder et al, 1995), which sequesters the cell survival factor insulin-like growth factor-1 (Baserga, 1994); the gene encoding the cathepsin-D protease (Wu et al, 1998) PAG608 which encodes a nuclear zinc ®nger protein (Israeli et al, 1997) and the human homolog of the Drosophila sina gene (Nemani et al, 1996). Recently a series of p53-induced genes (PIG genes) have been identi®ed that are predicted to encode proteins that could generate or respond to oxidative stress.…”

Quantitative Proteomic Analysis of Tumor Reversion in Multiple Myeloma Cells

“…In conclusion, we have developed the first biological model for studying MM reversion by using the H-1 parvovirus as a tool [7][8][9][10][11][12] to isolate revertants among millions of MM cells. The quantitative proteomics analysis described here identified many proteins that potentially affect MM reversion and implicate previously unconsidered pathways in the process of tumor reversion.…”

“…32 Different concentrations of the H1 parvovirus were used to infect RPMI8226 cells at a multiplicity of infection of 10-1000 plaque-forming units per cell using previously developed procedures. [7][8][9][10][11][12] The cytopathic effect of the virus caused massive cell death. After 10 weeks, the single clone which remained was expanded into a new culture and was infected with a second and then a third round of H1 parvovirus.…”

“…A series of reports have suggested an alternative approach, namely, to analyze what it is that causes a malignant cell to revert. [7][8][9][10][11][12] It is postulated that the molecular mechanisms for overriding cancer are present in such revertant cells and that it is possible to determine the key factors that reverse malignancy which are selected for in cancer cells. 11,12 An understanding of how this reversion happens may lead to the identification of targets that were not previously revealed by comparing normal and tumor cells.…”

“…To obtain such a system we applied Telerman and Amson's approach; namely, we used the H1 parvovirus, a small single-stranded DNA virus, to select for revertant cells among RPMI8226 myeloma cells. [8][9][10][11][12] After the stable MM revertant cell line was established, quantitative proteome analysis was performed to explore the possible mechanism and potential effector proteins in MM reversion by examining differential protein expression between parental MM cells and revertant cells.…”