DUSP22/LMW-DSP2 regulates estrogen receptor-alpha-mediated signaling through dephosphorylation of Ser-118.
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.
Sekine
Y
Y
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Ikeda
O
O
Hayakawa
Y
Y
Tsuji
S
S
Imoto
S
S
Aoki
N
N
Sugiyama
K
K
Matsuda
T
T
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D054637:Dual-Specificity Phosphatases; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D010768:Phosphoserine / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D010768:Phosphoserine; D004958:Estradiol; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010749:Phosphoprotein Phosphatases; C442824:DUSP22 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases