Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

Kazuki Ohno, Kosaku Okuda, Takashi Uehara

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Hydrogen sulfide (H2S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H2S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H2S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H2S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H2S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.

Original languageEnglish
Pages (from-to)245-249
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - Jan 2 2015


  • Cystathionine β-synthase
  • Hydrogen sulfide
  • Nitric oxide
  • PTEN
  • S-nitrosylation
  • S-sulfhydration

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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