Abstract

COLO, Georgina P.; RUBIO, María F.; ALVARADO, Cecilia V.  and  COSTAS, Mónica A.. RAC3 nuclear receptor co-activator has a protective role in the apoptosis induced by different stimuli. Medicina (B. Aires) [online]. 2007, vol.67, n.5, pp.465-468. ISSN 0025-7680.

RAC3 belongs to the family of p160 nuclear receptors coactivators and it is over-expressed in several tumors. We have previously shown that RAC3 is a NF-k;B coactivator. In this paper, we investigated the role of RAC3 in cell-sensitivity to apoptosis, using H₂O₂ in the human embryonic kidney cell line (HEK293), and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in a human chronic myeloid leukemia cell line (K562) naturally resistant to TRAIL. We observed that the tumoral K562 cells have high levels of RAC3 if compared with the non-tumoral HEK293 cells. The normal or transfected coactivator over-expression inhibits apoptosis through a diminished caspase activity and AIF nuclear translocation, increased NF-k;B, AKT and p38, and decreased ERK activities. In contrast, inhibition of RAC3 by siRNA induced sensitivity of K562 to TRAIL-induced apoptosis. Such results suggest that over-expression of RAC3 contributes to tumor development through molecular mechanisms that do not depend strictly on acetylation and/or steroid hormones, which control cell death. This could be a possible target for future tumor therapies.

Keywords : Apoptosis; NF-k;B; Nuclear receptor coactivators.

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