An investigation of p53’s differential activation of cell cycle arrest and apoptosis

The p53 tumour suppressor protein lies at the hub of a very complex network of cellular pathways including apoptosis, cell cycle arrest, DNA repair and cellular senescence. However, the mechanism of why and how p53 switches between apoptosis and cell cycle arrest, thereby determining a cell’s fate,...

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Main Author: Zhang, Yuan
Format: Thesis
Language:English
Published: Curtin University 2008
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/1577
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author Zhang, Yuan
author_facet Zhang, Yuan
author_sort Zhang, Yuan
building Curtin Institutional Repository
collection Online Access
description The p53 tumour suppressor protein lies at the hub of a very complex network of cellular pathways including apoptosis, cell cycle arrest, DNA repair and cellular senescence. However, the mechanism of why and how p53 switches between apoptosis and cell cycle arrest, thereby determining a cell’s fate, remains a mystery to us. To enable us to investigate this ability of p53 to switch between cell cycle arrest and apoptosis, we developed a model which demonstrates similar p53 expression patterns but different functional outcomes. Treating cells with Cisplatin (a common chemotherapeutic drug) and Nutlin-3 (an MDM-2 inhibitor) results in similar high levels of p53 accumulation but different cellular responses. Cisplatin-treated cells undergo apoptosis while Nutlin-treated cells enter cell cycle arrest. Using this model, we explored the localization of p53 and in particular a C-terminal Ser 392 moiety in an attempt to identify how p53 is able to preferentially activate cell cycle arrest or apoptotic pathway.
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spelling curtin-20.500.11937-15772017-02-20T06:37:42Z An investigation of p53’s differential activation of cell cycle arrest and apoptosis Zhang, Yuan apoptosis nutlin-3 p53 tumour suppressor protein cisplatin cell cycle arrest differential activation The p53 tumour suppressor protein lies at the hub of a very complex network of cellular pathways including apoptosis, cell cycle arrest, DNA repair and cellular senescence. However, the mechanism of why and how p53 switches between apoptosis and cell cycle arrest, thereby determining a cell’s fate, remains a mystery to us. To enable us to investigate this ability of p53 to switch between cell cycle arrest and apoptosis, we developed a model which demonstrates similar p53 expression patterns but different functional outcomes. Treating cells with Cisplatin (a common chemotherapeutic drug) and Nutlin-3 (an MDM-2 inhibitor) results in similar high levels of p53 accumulation but different cellular responses. Cisplatin-treated cells undergo apoptosis while Nutlin-treated cells enter cell cycle arrest. Using this model, we explored the localization of p53 and in particular a C-terminal Ser 392 moiety in an attempt to identify how p53 is able to preferentially activate cell cycle arrest or apoptotic pathway. 2008 Thesis http://hdl.handle.net/20.500.11937/1577 en Curtin University fulltext
spellingShingle apoptosis
nutlin-3
p53 tumour suppressor protein
cisplatin
cell cycle arrest
differential activation
Zhang, Yuan
An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title_full An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title_fullStr An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title_full_unstemmed An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title_short An investigation of p53’s differential activation of cell cycle arrest and apoptosis
title_sort investigation of p53’s differential activation of cell cycle arrest and apoptosis
topic apoptosis
nutlin-3
p53 tumour suppressor protein
cisplatin
cell cycle arrest
differential activation
url http://hdl.handle.net/20.500.11937/1577