Award details

Switching behaviour of PTEN activity

Reference	BBS/E/F/00044502
Principal Investigator / Supervisor	Dr Maria Traka
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	93,713
Status	Completed
Type	Institute Project
Start date	15/08/2014
End date	30/09/2015
Duration	13 months

Abstract

Phosphatase and tensin homologue (PTEN), a major tumour suppressor gene, can be inactivated by post-transcriptional modifications (1). PTEN converts phosphatidylinositol (3,4,5)-triphosphate (PIP3) to phosphatidylinositol(4,5)-biphosphate (PIP2), thereby directly opposing the activity of PI3K and downstream phosphorylation of AKT, a major orchestrator of cell growth and cell survival (2). Bistability is a fundamental phenomenon in nature and ensures the “decision” to start the chain of events is ultimate, preventing any non-viable “half” state (3,4). Analysing a minimal bistable system we have identified three necessary conditions for bistability: a positive feedback, a mechanism to filter out small stimuli and a mechanism to prevent explosions (of concentrations) by a negative feedback (5). We plan to test the hypothesis that high and low PTEN activity corresponds to two clearly distinctive states of cellular behaviour and that the transition from high to low PTEN activity is switch-like rather than linear. We intend to modulate PTEN activity by changing cell redox status, which inactivates PTEN through oxidation of cysteine residues (6,7). This would reflect the increase in oxidative stress seen by ageing and certain lifestyle factors, such as diet and lack of exercise. Aim of the project: The aim of this project is to determine whether oxidative stress results in loss of PTEN activity that has the characteristic of a bistable switch. To do this we will devise model(s) of PTEN activity as a result of increasing levels of ROS in healthy prostate cells. We will use SDS-PAGE and HPLC-MS based methods to determine PTEN oxidation status.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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