Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/34666
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dc.titleACTIVATING MUTANT P53: A DIRECTED EVOLUTION APPROACH
dc.contributor.authorGOH LENG PENG
dc.date.accessioned2012-09-12T18:00:53Z
dc.date.available2012-09-12T18:00:53Z
dc.date.issued2011-10-27
dc.identifier.citationGOH LENG PENG (2011-10-27). ACTIVATING MUTANT P53: A DIRECTED EVOLUTION APPROACH. ScholarBank@NUS Repository.
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/34666
dc.description.abstractThe tumor suppressor p53 plays a cardinal role in genomic stability and cancer prevention, and hence, realizing new cancer therapeutics lie in dissecting the multitude of complex, yet intricate, cellular networks involving p53. Because inactivating mutations in p53 are a direct cause of 50% of all human cancers, reactivating mutant p53 has long been an attractive approach towards possible cancer treatments. In this current study, we selected 7 p53 activating peptides (pap) for p53 hotspot mutants by exploiting the In-Vitro Compartmentalization selection platform. Additionally, a sensitive, non-radioactive, real-time PCR based p53-DNA binding assay was developed with the purpose of validating these peptides. The DNA binding assay could accurately measure binding between different IVT synthesized p53 variants and nano-molar concentrations of DNA response elements (REs). Data from the DNA-binding assay, together with other in-vitro assays, indicate that the paps interact directly with mutant p53 and reactivate sequence-specific DNA binding.
dc.language.isoen
dc.subjectp53, cancer, reactivation, DNA binding, peptides
dc.typeThesis
dc.contributor.departmentMEDICINE
dc.contributor.supervisorSIR DAVID LANE
dc.description.degreePh.D
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
dc.identifier.isiutNOT_IN_WOS
Appears in Collections:Ph.D Theses (Open)

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