S-Nitrosylation of mitogen activated protein kinase phosphatase-1 suppresses radiation-induced apoptosis.

Abstract

Radiotherapy is a key modality for head and neck cancer (HNC) treatment. Mitogen activated protein kinase phosphatase-1 (MKP-1) protein levels are elevated in various tumors and are negatively correlated with efficacy of chemo- or radio-therapy. However, the mechanisms underlying the moderate radiosensitivity of HNC and the increased MKP-1 protein levels are still dismal. Here we show that S-nitrosylation of MKP-1 on Cysteine 258 enhances MKP-1 protein stability, phosphatase activity, and MKP-1-mediated anti-apoptotic effect on HNC radiotherapy. Co-culturing MKP-1 transfected HNC cell lines with activated macrophages for mimicking the microenvironment of the irradiated cancer cells further confirms that S-nitrosylation-mediated increase of MKP-1 activity correlates with decrease of HNC radiosensitivity. Therefore, S-nitrosylation of MKP-1 presents a novel mechanism underlying the enhanced MKP-1 expression levels and MKP-1-mediated radio-resistance in head and neck cancer.

• Authors: Weiping Guan, Jibin Sha, Xiaojuan Chen, Yaling Xing, Jinqi Yan, Zhaoqing Wang
• Journal: Cancer letters (Cancer Lett) Vol. 314 Issue 2 Pg. 137-46 (Jan 28 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22014408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Nitric Oxide Synthase Type II
• JNK Mitogen-Activated Protein Kinases
• DUSP1 protein, human
• Dual Specificity Phosphatase 1
• Dusp1 protein, mouse

Topics

• Animals
• Apoptosis (radiation effects)
• Cell Line
• Cell Line, Tumor
• Dual Specificity Phosphatase 1 (genetics, physiology)
• Gamma Rays
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Nitric Oxide Synthase Type II (metabolism)
• Radiation Tolerance