DUSP22/LMW-DSP2 regulates estrogen receptor-alpha-mediated signaling through dephosphorylation of Ser-118

Oncogene. 2007 Sep 6;26(41):6038-49. doi: 10.1038/sj.onc.1210426. Epub 2007 Mar 26.


In the previous study, we demonstrated the involvement of dual specificity phosphatase 22 (DUSP22/LMW-DSP2) in regulating the leukemia inhibitory factor/interleukin-6/signal transducer and activator of transcription 3-mediated signaling pathway. In this study, we show beta-estradiol (E2)-induced DUSP22 mRNA expression in estrogen receptor alpha (ERalpha)-positive breast cancer cells, whereas E2-induced phosphorylation and activation of ERalpha was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. Furthermore, small-interfering RNA-mediated reduction of DUSP22 expression enhanced ERalpha-mediated transcription and endogenous gene expression. In fact, DUSP22 associated with ERalpha in vivo and both endogenous proteins interacted in ERalpha-positive breast cancer T47D cells. These results strongly suggest that DUSP22 acts as a negative regulator of the ERalpha-mediated signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Dual-Specificity Phosphatases
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / drug effects
  • Estrogen Receptor alpha / physiology*
  • Female
  • HeLa Cells
  • Humans
  • Mitogen-Activated Protein Kinase Phosphatases
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoserine / metabolism*
  • Polymerase Chain Reaction
  • Protein Tyrosine Phosphatases / genetics*
  • RNA, Messenger / genetics
  • Signal Transduction
  • Transcriptional Activation / physiology*
  • Tumor Cells, Cultured


  • Estrogen Receptor alpha
  • RNA, Messenger
  • Phosphoserine
  • Estradiol
  • Mitogen-Activated Protein Kinase Phosphatases
  • Phosphoprotein Phosphatases
  • DUSP22 protein, human
  • Dual-Specificity Phosphatases
  • Protein Tyrosine Phosphatases