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S-nitrosylation of ERK inhibits ERK phosphorylation and induces apoptosis

Xiujing Feng1, Tingzhe Sun, Yuncheng Bei

  • 1State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, China.

Scientific Reports
|May 10, 2013
PubMed

Insights

Nitric oxide (NO) induces S-nitrosylation of extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase (MAPK). This process inhibits ERK phosphorylation, promoting apoptosis and potentially impacting tumor development.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Extracellular signal-regulated kinase (ERK), part of the mitogen-activated protein kinases (MAPK) superfamily, is frequently upregulated in tumors.
  • The precise role of ERK in tumor progression remains incompletely understood.
  • Nitric oxide (NO) is a signaling molecule with diverse cellular functions.

Purpose of the Study:

  • To investigate the regulatory mechanism of ERK by nitric oxide (NO).
  • To elucidate the role of ERK S-nitrosylation in apoptosis and tumor development.

Main Methods:

  • Studied the effect of NO on ERK activity and phosphorylation.
  • Utilized fluorescence staining to assess apoptosis.
  • Employed NO scavenger Haemoglobin (HB) and an S-nitrosylation-deficient ERK mutant (C183A) to validate findings.

Main Results:

  • Demonstrated that ERK undergoes S-nitrosylation mediated by NO.
  • Showed that ERK S-nitrosylation inhibits its phosphorylation and induces apoptosis.
  • Confirmed that NO's proapoptotic effect via S-nitrosylation is reversible by HB and abolished by the C183A mutant.
  • Identified Cys(183) as a potential S-nitrosylation site on ERK.

Conclusions:

  • NO-mediated S-nitrosylation of ERK is a novel regulatory mechanism controlling its activity.
  • This pathway inhibits ERK phosphorylation, promoting apoptosis and offering insights into tumor suppression.
  • ERK S-nitrosylation represents a potential target for cancer therapy.

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