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|Title:||Molecular interaction of tumor suppressor protein p53 and anti-apoptotic proteins Bcl-2 and Bcl-XL.||Authors:||Yoon, Ho Sup.||Keywords:||DRNTU::Science::Biological sciences::Molecular biology||Issue Date:||2007||Abstract:||Emerging evidences suggest that transcription-independent mechanism of p53 appears to make an important contribution to the overall p53-dependent apoptosis. The molecular interaction between Bel-XL and p53 is critical for this regulation. To understand the nature of the molecular recognition between p53 and Bel-XL, we first demonstrated the molecular interaction by co-expressing and purifying the complex. Second, to define the binding interface of the molecular interaction, which is not previously characterized, we employed a NMR-based binding study, showing that the binding site on Bel-XL is located in the region including a4, the N- and C-termini of a3, the N-terminus of a5, and the central part of a2. To further probe this observation, we then performed fluorescence resonance energy transfer (FRET) assay in cells. The FRET efficiency detected between the donor and acceptor molecules suggests the presence of molecular interaction of p53NTD with Bel-XL in cells. Taken together, our data suggest that p53NTD physically interacts with Bel-XL. To define molecular basis of the molecular interaction in detail, we further identified part in p53NTD required for the interaction with Bel-XL. Through site-directed mutagenesis, affinity binding, and NMR experiments, we showed that the MDM2-binding region (residues from S15 to N29) in the transactivation domain ofp53 (p53TAD) is identified as a novel binding motif for Bel-XL. Conformational change is observed in the peptide representing p53TAD upon forming a complex with Bel-XL. In addition, BH3 peptides of Bak and Bax compete in a binding assay against, suggesting that SN15 peptide and BH3 peptides can share a binding site in Bel-XL. Based on the results generated from our study a structural model for the molecular interaction between Bel-XL and the p53TAD peptide has been proposed.||URI:||http://hdl.handle.net/10356/41823||Fulltext Permission:||restricted||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Research Reports (Staff & Graduate Students)|
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