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

Abstract
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 β-estradiol (E2)-induced DUSP22 mRNA expression in estrogen receptor α (ERα)-positive breast cancer cells, whereas E2-induced phosphorylation and activation of ERα was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. Furthermore, small-interfering RNA-mediated reduction of DUSP22 expression enhanced ERα-mediated transcription and endogenous gene expression. In fact, DUSP22 associated with ERα in vivo and both endogenous proteins interacted in ERα-positive breast cancer T47D cells. These results strongly suggest that DUSP22 acts as a negative regulator of the ERα-mediated signaling pathway.