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 sigma, the p53 target gene, is a unique tumor suppressor. We here report 14-3-3 sigma as a transforming growth factor-beta (TGF-beta) target gene. In mammary epithelial cells, TGF-beta selectively induced expression of 14-3-3 sigma 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-beta 1-induced 14-3-3 sigma expression. Our data provides the first evidence that 14-3-3 sigma is a Smad3-dependent target gene of TGF-beta 1. (C) 2013 Elsevier Inc. All rights reserved.