The cytokine transforming growth factor-β (TGF-β) regulates cell growth and differentiation by controlling gene expression. This receptor-to-nucleus signaling pathway is facilitated by a family of Smad proteins that moves from the cytoplasm into the nucleus to affect transcription. Kim et al. report that a nuclear protein called Smad interacting protein 1 (SNIP1) suppresses TGF-β signaling by binding to Smad4, an essential mediator of TGF-β signaling responses. This interaction requires the amino terminus of SNIP1, which also harbors a nuclear localization signal. Binding to SNIP1 competes with Smad4 association with the transcriptional coactivator CBP/p300. The authors propose that TGF-β signaling is thus inhibited when Smad4 is sequestered by SNIP1.
Kim, R.H., Wang, D., Tsang, M., Martin, J., Huff, C., de Caestecker, M.P., Parks, W.P., Meng, X., Lechleider, R.J., Wang, T., and Roberts, A.B. (2000) A novel Smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-β signal transduction. Genes Dev. 14: 1605-1616. [Abstract] [Full Text]