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Deadly Combination of Smad and AP-1

Science's STKE  21 Nov 2000:
Vol. 2000, Issue 59, pp. tw5
DOI: 10.1126/stke.2000.59.tw5

Transforming growth factor-β (TGF-β) can stimulate multiple biological responses from proliferation to cell death. But the mechanisms by which it leads to apoptosis have been unclear. The Smad proteins are well known mediators of the transcriptional effects of TGF-β. This cytokine also increases expression of components of AP-1 transcription complexes. Yamamura et al. present evidence that cooperative effects of Smad3 and Smad7 with the JunD:FosB form of the AP-1 complex are necessary for TGF-β-mediated apoptosis. The results provide another example where signals from distinct pathways are coordinated through interaction of Smads with transcriptional regulators that are sensitive to other signaling pathways. The authors note that loss of such apoptotic effects of TGF-β could contribute to tumor formation.

Yamamura. Y., Hua, X., Bergelson, S., and Lodish, H.F. (2000) Critical role of Smads and AP-1 complex in transforming growth factor-beta-dependent apoptosis. J. Biol. Chem. 275: 36295-36302. [Abstract] [Full Text]

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