Cell proliferation

Cell proliferation: Interfering with Smads

Science's STKE  26 Oct 1999:
Vol. 1999, Issue 5, pp. tw6
DOI: 10.1126/stke.1999.5.tw6

Unregulated cell growth results in tumor production; therefore, it is important to identify developmental factors that regulate cell growth. Transforming growth factor-beta (TGF-β) regulates cell growth and differentiation through receptor-mediated phosphorylation of Smad proteins. These Smad proteins in turn form protein complexes and enter the cell's nucleus to activate the transcription of target genes. Stroschein et al. have identified a new player, SnoN, in TGF-β signaling. In the absence of TGF-β, the SnoN oncoprotein binds to a Smad2/Smad4 complex and recruits a transcription co-repressor, thus inhibiting transcription activation. When TGF-β is present, Smad3 triggers the degradation of SnoN and transcription activation resumes. Finally, a negative-feedback mechanism is present in which TGF-β stimulates SnoN production, which then represses the transcription activation function of the Smad complex once again. SnoN is found in various carcinomas. Hence, the transforming activity of SnoN may be explained by its interference with the role of TGF-β in inhibiting cell growth.

Stroschein, S.L., Wang, W., Zhou, S., Zhou, Q., and Luo, K. (1999) Negative feedback regulation of TGF-signaling by the SnoN oncoprotein. Science 286: 771 - 774. [Abstract] [Full Text]