1. Estrogen Inhibits Transforming Growth Factor β Signaling by Promoting Smad2/3 Degradation.
- Author
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Ito, Ichiaki, Hanyu, Aki, Wayama, Mitsutoshi, Goto, Natsuka, Katsuno, Yoko, Kawasaki, Shohei, Nakajima, Yuka, Kajiro, Masashi, Komatsu, Yoko, Fujimura, Akiko, Hirota, Ryuichi, Murayama, Akiko, Kimura, Keiji, Imamura, Takeshi, and Yanagisawa, Junn
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ESTROGEN receptors , *REGULATION of cell growth , *TRANSFORMING growth factors , *NUCLEAR receptors (Biochemistry) , *CELL communication , *UBIQUITIN , *PHYSIOLOGY - Abstract
Estrogen is a growth factor that stimulates cell proliferation. The effects of estrogen are mediated through the estrogen receptors, ERα and ERβ, which function as ligand-induced transcription factors and belong to the nuclear receptor superfamily. On the other hand, TGF-β acts as a cell growth inhibitor, and its signaling is transduced by Smads. Although a number of studies have been made on the cross-talk between estrogen/ERa and TGF-β/Smad signaling, whose molecular mechanisms remain to be determined. Here, we show that ERα inhibits TGF-β signaling by decreasing Smad protein levels. ERα-mediated reductions in Smad levels did not require the DNA binding ability of ERα, implying that ERα opposes the effects of TGF-β via a novel non-genomic mechanism. Our analysis revealed that ERα formed a protein complex with Smad and the ubiquitin ligase Smurf, and enhanced Smad ubiquitination and subsequent degradation in an estrogen-dependent manner. Our observations provide new insight into the molecular mechanisms governing the non-genomic functions of ERα, [ABSTRACT FROM AUTHOR]
- Published
- 2010
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