Exploring nanobodies interrupting the interaction between p53 and MDM4

Sarıyar, Sanem (2019) Exploring nanobodies interrupting the interaction between p53 and MDM4. [Thesis]

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The p53 protein is considered as the guardian of the genome thanks to its important tumor suppressor roles such as cell-cycle arrest, apoptosis and senescence. Because these roles are extremely vital, the p53 pathway is strictly regulated. During unstressed conditions, p53 protein levels are kept in control by both ubiquitination of the p53 protein and inhibition of its transcriptional activity through the MDM2 and MDM4 proteins, respectively. Although MDM2 is the main modulator of p53 activity, there is a collaboration between MDM2 and MDM4 proteins to enable the control of p53. Thus, MDM4 is as important as MDM2 in this mechanism. In most human cancers, there is either a mutation in the Tp53 gene or an overexpression of its negative regulators. Thus, targeting the p53-MDM2-MDM4 interplay is one of the main aims of cancer therapeutics. Also, in some cancers, where there is overexpression of negative regulators, the use of inhibitors for only MDM2 is not enough to activate the p53 protein. For this reason, exploring inhibitors for MDM4 are vital for therapy. In this study, we aimed to optimize the purification of in silico designed nanobodies targeting the MDM4-p53 interaction and test their affinity and effectiveness by surface plasmon resonance (SPR) and a fluorescent two-hybrid (F2H) assay.
Item Type: Thesis
Uncontrolled Keywords: p53 / MDM4 interaction. -- Nanobodies. -- Nanobody purification. -- Fluorescent two-hybrid assay. -- Surface plasmon resonance. -- p53/MDM4 etkileşimi. -- Nanobodiler. -- Nanobodi saflaştırılması. -- Floresan ikili hibrit tekniği. -- Yüzey plasmon rezonans.
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: IC-Cataloging
Date Deposited: 26 Aug 2019 14:19
Last Modified: 26 Apr 2022 10:30
URI: https://research.sabanciuniv.edu/id/eprint/39119

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