Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins


Phosphatase and tensin homolog (PTEN) is involved in a number of different cellular processes including metabolism, apoptosis, cell proliferation and survival. It is a redox-sensitive dual-specificity protein phosphatase that acts as a tumor suppressor by negatively regulating the PI3K/Akt pathway. While direct evidence of redox regulation of PTEN downstream signaling has been reported, the effect of PTEN redox status on its protein-protein interactions is poorly understood. PTEN-GST in its reduced and a DTT-reversible H2O2-oxidized form was immobilized on a glutathione-sepharose support and incubated with cell lysate to capture interacting proteins. Captured proteins were analyzed by LC-MSMS and comparatively quantified using label-free methods. 97 Potential protein interactors were identified, including a significant number that are novel. The abundance of fourteen interactors was found to vary significantly with the redox status of PTEN. Altered binding to PTEN was confirmed by affinity pull-down and Western blotting for Prdx1, Trx, and Anxa2, while DDB1 was validated as a novel interactor with unaltered binding. These results suggest that the redox status of PTEN causes a functional variation in the PTEN interactome. The resin capture method developed had distinct advantages in that the redox status of PTEN could be directly controlled and measured.

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Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( Funding: EPSRC (EP/I017887/1 Cross-Disciplinary Research Landscape Award). Data associated with this paper can be obtained by contacting the corresponding author. Supplementary material avaialble on the journal website
Uncontrolled Keywords: DNA-binding proteins,disulfides,glutathione,HCT116 cells,oxidation-reduction,PTEN phosphohydrolase,peroxiredoxins,proteomics,signal transduction,thioredoxins,Biochemistry,Physiology (medical)
Publication ISSN: 1873-4596
Last Modified: 27 Jun 2024 08:43
Date Deposited: 16 Dec 2015 11:40
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2016-01-01
Published Online Date: 2015-11-10
Accepted Date: 2015-11-01
Authors: Verrastro, Ivan
Tveen-Jensen, Karina
Woscholski, Rudiger
Spickett, Corinne M. (ORCID Profile 0000-0003-4054-9279)
Pitt, Andrew R. (ORCID Profile 0000-0003-3619-6503)



Version: Published Version

License: Creative Commons Attribution

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