Dual-site interactions of p53 protein transactivation domain with anti-apoptotic bcl-2 family proteins reveal a highly convergent mechanism of divergent p53 pathways

Abstract

Background: Interactions between p53 and Bcl-2 family proteins serve a critical role in transcription-independent p53 apoptosis. Results: We studied the interactions of p53TAD2 with anti-apoptotic Bcl-2 family proteins at the atomic level by NMR, mutagenesis, and structure calculation. Conclusion: Bcl-XL/Bcl-2, MDM2, and CBP/p300 share similar modes of binding to the dual p53TAD motifs. Significance: Dual-site interaction of p53TAD is a highly conserved mechanism in the transcription-dependent and transcription- independent p53 apoptotic pathways.