TAF6delta controls apoptosis and gene expression in the absence of p53.
BACKGROUND
Life and death decisions of metazoan cells hinge on the balance between the expression of pro- versus anti-apoptotic gene products. The general RNA polymerase II transcription factor, TFIID, plays a central role in the regulation of gene expression through its core promoter recognition and co-activator functions. The core TFIID subunit TAF6 acts in vitro as an essential co-activator of transcription for the p53 tumor suppressor protein. We previously identified a splice variant of TAF6, termed TAF6delta that can be induced during apoptosis.


RESULTS
To elucidate the impact of TAF6delta on cell death and gene expression, we have employed modified antisense oligonucleotides to enforce expression of endogenous TAF6delta. The induction of endogenous TAF6delta triggered apoptosis in tumor cell lines, including cells devoid of p53. Microarray experiments revealed that TAF6delta activates gene expression independently of cellular p53 status.


CONCLUSIONS
Our data define TAF6delta as a pivotal node in a signaling pathway that controls gene expression programs and apoptosis in the absence of p53.
Wilhelm
Emmanuelle
E
RNA Group, Département de microbiologie et d'infectiologie, Faculté de médecine et sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Pellay
François-Xavier
FX
Benecke
Arndt
A
Bell
Brendan
B
D017209:Apoptosis; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D015398:Signal Transduction; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009841:Oligonucleotides; C084977:TAF6 protein, human; D035381:TATA-Binding Protein Associated Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53