Transcription regulation

Stopping Smads in the nucleus

Science's STKE  28 Sep 1999:
Vol. 1999, Issue 1, pp. tw2
DOI: 10.1126/stke.1999.1.tw2

One potent effect of the cytokine transforming growth factor-β (TGFβ) is to arrest growth in certain cell types. Upon activation by its ligand, the TGFβ receptor induces the formation of a heterocomplex of the Smad 2, 3, and 4 proteins in the cytosol. The Smad complex then translocates into the nucleus to activate TGFβ -responsive genes. Luo et al. report that a nuclear protein called Ski binds to and inhibits the Smad complex. Ski itself is a transcription regulator and is implicated in cell growth control. Ski expression repressed TGFβ-induced inhibition of cell growth. Smad-Ski interaction may therefore be one mechanism by which both TGFβ signaling is disabled and the transforming activity of Ski is promoted.

Luo, K., Stroschein, S.L., Wang, W., Chen, D., Martens, E., Zhou, S., Zhou, Q. (1999) The Ski oncoprotein interacts with Smad proteins to repress TGFβ?signaling. Genes Dev. 13: 2196-2206. [Abstract] [Full Text]