A function in apoptosis other than transactivation inherent in the NH2-terminal domain of p53.
p53-mediated programmed cell death (PMCD) often requires an intact transactivation domain of the p53 tumor suppressor and is therefore usually interpreted to rely upon the transactivation of genes. As a notable exception, murine GHFT1 cells have been documented to perish in a p53-dependent manner even in the presence of transcription inhibitor actinomycin D (Act D) and have since served as one model system for transactivation-independent apoptosis. We report here that p53 transactivation domain mutant Q22,S23 nonetheless fails to mediate apoptosis in these cells as efficiently as wild-type p53. This suggests that some function of the NH2-terminal domain other than the transactivation of genes supports PMCD of GHFT1 cells. To substantiate this suggestion, we employed a p53 whose transactivation domain had been replaced with the one of VP16, which acts through the same elements of the basal transcription machinery. Although the hybrid was fully competent for transactivation, it was impaired for the mediation of apoptosis to the same extent as mutant Q22,S23. Thus, a function of the transactivation domain other than the binding to the transcription co-activators hTAF(II)31 and 70 is required for the efficient induction of apoptosis in GHFT1 cells.
Theis
S
S
Department of Virology, University of the Saarland, Homburg/Saar, Germany.
Atz
J
J
Mueller-Lantzsch
N
N
Roemer
K
K
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010446:Peptide Fragments / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D010446:Peptide Fragments; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA