[RAC3 nuclear receptor co-activator has a protective role in the apoptosis induced by different stimuli].
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-kappaB 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-kappaB, 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.
Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, IDIM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Georgina P
GP
Coló
María F
MF
Rubio
Cecilia V
CV
Alvarado
Mónica A
MA
Costas
D017209:Apoptosis / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007668:Kidney / Q000166:cytology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*
C411563:RAC3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D014157:Transcription Factors; D020744:rac GTP-Binding Proteins