Negative Feedback Regulation of TGF-β Signaling by the SnoN Oncoprotein

作者：Shannon L. Stroschein, Wei Wang, Sharleen Zhou, Qiang Zhou, Kunxin Luo · 发表于：Science · 年份：1999 · DOI：10.1126/science.286.5440.771 · 被引用次数：494 · 研究领域：TGF-β signaling in diseases、Cancer-related gene regulation、FOXO transcription factor regulation

Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.