14-3-3 σ is a new target up-regulated by transforming growth factor-β1 through a Smad3-dependent mechanism.

The seven members of the human 14-3-3 family play crucial roles in a diverse range of cellular responses including cell cycle progression, DNA damage checkpoint, and apoptosis. One particular isoform, 14-3-3 σ, the p53 target gene, is a unique tumor suppressor. We here report 14-3-3 σ as a transforming growth factor-beta (TGF-β) target gene. In mammary epithelial cells, TGF-β selectively induced expression of 14-3-3 σ at both mRNA and protein levels, and this induction was dependent on Smad3 not on p53. In addition, blockade of non-canonical Smad-independent pathways, including MAP kinases and Rho GTPases, did not affect the TGF-β1-induced 14-3-3 σ expression. Our data provides the first evidence that 14-3-3 σ is a Smad3-dependent target gene of TGF-β1.