Mapping oxidative modifications of PTEN

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The oxidation of certain amino acids in proteins can cause many effects including aggregation and fragmentation, as well as affecting the function such catalytic activity and protein interactions. Therefore, it is not surprising that oxidative modification of proteins is predicted to be involved in the development of many pathologies, including neurodegeneration and cancer. Hence, the development of methods to detect oxidative damage is of significant medical relevance. Our research focuses on developing mass spectrometric techniques including precursor ion scanning, neutral loss, targeted MS, high mass accuracy MS and multiple reaction monitoring to determine accurately the presence and localization of oxidative modifications. Our initial work focuses on PTEN (phosphatase and tensin homolog on chromosome 10), a phosphatase that is sensitive to oxidation involved in the control of apoptosis by negatively regulating the Akt pathway. Using mass spectrometry we have successfully detected several modified residues in PTEN after treatment with hypochlorous acid (HOCl) and 3-morpholinosydnonimine (SIN-1, a peroxynitrite donor), including hydroxytyrosine, chlorotyrosine and nitrotyrosine. These modifications map to a number of regions in PTEN including the putative protein interaction binding domains and near to the PTEN active site. We have also detected oxidation products of a cysteine residue involved in the redox regulation of PTEN. We are correlating these modifications with changes in PTEN activity and protein interactions to begin to understand better how oxidative modifications can alter protein function and affect cellular signalling. Acknowledgements This Project is funded by the EPSRC (EP/I07887) and Aston University.

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Original languageEnglish
Article number0576
Pages (from-to)S213
Number of pages1
JournalFree Radical Biology and Medicine
Volume53
Issue numberSupplement 1
DOIs
Publication statusPublished - Sep 2012
EventSociety for Free Radical Research International 16th Biennial Meeting - Imperial College London, London, United Kingdom
Duration: 6 Sep 20129 Sep 2012

Employable Graduates; Exploitable Research

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