ד"ר אלה פישמן - Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

מבוסס על מאמרם של ד"ר אלה פישמן, Andrei V Budanov, Tzipora Shoshani, Alexander Faerman, Elena Zelin, Iris Kamer, Hagar Kalinski, Svetlana Gorodin, Ayelet Chajut, Paz Einat, Rami Skaliter, Andrei V Gudkov, Peter M Chumakov and Elena Feinstein

A prolonged oxygen deprivation can result in many serious pathological conditions like stroke and heart attack. The development of drugs to prevent this condition focuses on finding out genes that regulate programmed cell death of cells in the oxygen deprived tissues. Many genes involved in this pathway were identified using cDNA microarray hybridization technique. One such gene Hi95 was chosen for further analysis. This gene was cloned and was sequenced to reveal its structure. The Hi95 gene was found to be structurally very close to PA26 gene, a member of GADD family that responds to tumor repressor gene p53 and thus can be linked with cancer due to its ability to slow down the growth of cancer cells by damaging their DNA. Apart from this structural similarity, the functional properties of Hi95 were also found to be similar to GADD family members. The roles of Hi95 were elucidated in both cell line system and in tissues. The Hi95 gene sometimes works independent of the effect of tumor repressor gene p53 to slow down cancer cells growth. These roles of Hi95 in cells were validated after its over-expression which led to cell death and to reduced responses of cells towards treatments that damage their DNAs. But in some stress conditions, Hi95 gene showed opposite actions and its over-expression in certain conditions protected the cells not only from oxygen or glucose deprivation but from the toxic effects of H₂O₂ too. Therefore Hi95 is linked to the regulation of cell growth and survival. The characterization of Hi95 helps researchers in finding out novel therapeutics against stroke and heart attack. Thus the identification of various cell signaling pathways that are regulated by Hi95 gene seems to be an attractive strategy to find out approaches that can modulate the responses of cells towards various kinds of stress.