Study of the apoptotic process and the effects induced by TAF7 gene expression silencing using sirna

Understanding the immunopathogenesis and biology of HIV infection is of great importance to introduce new therapeutic strategies and prophylactic vaccines. Tat is one of the nine genes encoded in the HIV genome and its functions are can be grouped under 3 topics: 1) The transcriptional transactivation of the provirus 2) Inhibition of the host genes at the transcriptional level mainly 3) Inducing apoptosis in host cells. It has been proposed that TAF7 ? a component of the general transcription factor TFIID - could be a functional homologue of HIV Tat. TAF7 has been shown to support elongation and to inhibit transcription by mechanisms very similar to HIV Tat. But Tat there are no studies reporting a role for TAF7 in apoptosis. The identification of the apoptotic pathways is very important to health sciences. The mechanism of the general transcriptional blockage observed during apoptosis remains unknown. Previous reports have suggested that TAF7 acts as a transcriptional checkpoint regulator. In accordance with this model we hypothesize that the transcriptional blockage is an integral part of the apoptotic process and is induced via TAF7. To test this hypothesis TAF7 expression was inhibited by siRNA in cell lines induced with radiation, MGBG and etoposide. A 4-6 fold reduction in apoptotic death was observed in the TAF7 siRNA group when compared to controls. On contrast TAF7 induced apoptosis in cells when overexpressed by stabilizing microtubule polymerization; a mechanism very similar to HIV Tat. This is the first study reporting a role for TAF7 and the transcriptional machinery in apoptosis.