BIM and NOXA are mitochondrial effectors of TAF6?-driven apoptosis.

ABSTRACT: TAF6? is a pro-apoptotic splice variant of the RNA polymerase II general transcription factor, TAF6, that can dictate life vs. death decisions in animal cells. TAF6? stands out from classical pro-apoptotic proteins because it is encoded by a gene that is essential at the cellular level, and because it functions as a component of the basal transcription machinery. TAF6? has been shown to modulate the transcriptome landscape, but it is not known if changes in gene expression trigger apoptosis nor which TAF6?-regulated genes contribute to cell death. Here we used microarrays to interrogate the genome-wide impact of TAF6? on transcriptome dynamics at temporal resolution. The results revealed changes in pro-apoptotic BH3-only mitochondrial genes that correlate tightly with the onset of cell death. These results prompted us to test and validate a role for the mitochondrial pathway by showing that TAF6? expression causes cytochrome c release into the cytoplasm. To further dissect the mechanism by which TAF6? drives apoptosis, we pinpointed BIM and NOXA as candidate effectors. siRNA experiments showed that both BIM and NOXA contribute to TAF6?-dependent cell death. Our results identify mitochondrial effectors of TAF6?-driven apoptosis, thereby providing the first of mechanistic framework underlying the atypical TAF6? apoptotic pathway's capacity to intersect with the classically defined apoptotic machinery to trigger cell death.

SUBMITTER: Delannoy A 

PROVIDER: S-EPMC5833734 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature