dc.contributor.authorXu, Huibin
dc.identifier.citationXu, H. B. (2008). Biochemical and structural studies on the molecular interaction between P53 transcriptional activation domain and anti-apoptotic protein BCL-XL. Doctoral thesis, Nanyang Technological University, Singapore.
dc.description.abstractThis is due to its critical role in the regulation of apoptosis and control of cancer formation. p53 is believed to be the most important tumor suppressor protein and abnormality of p53 causes cancers and many other diseases. Functional studies revealed that p53 is an important transcriptional activator. It initiates transcription of many pro-apoptosis genes, which activate multiple apoptotic pathways and finally induce cell death. Besides its transcription-dependent apoptosis activity, the apoptotic activity of p53 out of the nuclei was also observed and draws attention. p53 interacts with the anti-apoptotic proteins, Bcl-2/XL, and induces mitochondria-mediated apoptosis. The transcription activity of p53 is not involved in this pathway, suggesting transcription-independent mechanism of p53. The p53/Bcl-2 and p53/Bcl-XL interaction were then investigated by different groups. The DNS binding domain of p53 was believed to be the binding site in the p53/Bcl-XL interaction. However, there is no detail structure information of the complex so far. In this study, we identified a novel binding site on p53 N-terminal domain (NTD) for Bcl-XL. The p53 NTD/ Bcl-XL complex was observed and obtained in a co-expression system in E.coli. NMR study also confirmed this physical interaction in vitro. We also showed their interaction in mammalian cells using FRET assay. A preliminary binding interface on Bcl-XL was suggested according to the 1H-15N 2D HSQC NMR titration experiments.en_US
dc.format.extent210 p.en_US
dc.subjectDRNTU::Science::Biological sciences::Biochemistryen_US
dc.titleBiochemical and structural studies on the molecular interaction between P53 transcriptional activation domain and anti-apoptotic protein BCL-XLen_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.supervisorYoon, Ho Supen_US
dc.description.degreeDOCTOR OF PHILOSOPHY (SBS)en_US

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