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Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response

Oncogene volume 27, pages 4877–4887 (2008)Cite this article

Abstract

Sulfiredoxin (Srx) is one of a family of low molecular weight sulfur containing proteins linked with maintenance of cellular redox balance. One function of Srx is the reduction of cysteine sulfinic acid to sulfenic acid in proteins subject to oxidative stress. Other redox active protein families have multiple functions in regulating redox and controlling proliferation/death pathways; increased Srx has been linked with oncogenic transformation. To explore the biological functions of Srx in tumors, we established cell lines that overexpress Srx. Enhanced levels of Srx promoted cell proliferation and enhanced cell death following cisplatin. Srx overexpression triggered an alteration in expression and phosphorylation of cell cycle regulators p21, p27 and p53; stabilized the phosphatase PTEN and, importantly, interacted directly with, and enhanced the activity of, phosphatase PTP1B. In turn, this promoted Src kinase activity by dephosphorylating its inhibitory tyrosine residue (Y530). Srx expression was stimulated by cell exposure to certain growth factors. These data support a role for Srx in controlling the phosphorylation status of key regulatory kinases through effects upon phosphatase activity with an ultimate effect on pathways that influence cell proliferation.

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Acknowledgements

We thank Dr Carola A Neumann for providing retroviral vectors and packaging cells. This work was supported by a postdoctoral fellowship grant (T32 CA119945-02) to KL and by CA08660 to KDT. We thank the Drug Metabolism and Pharmacokinetics facility for GSH measurements.

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  1. Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC, USA

    K Lei & K D Tew

  2. Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, USA

    D M Townsend

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  1. K Lei
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Correspondence to K D Tew.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lei, K., Townsend, D. & Tew, K. Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response. Oncogene 27, 4877–4887 (2008). https://doi.org/10.1038/onc.2008.132

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