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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.

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