14-3-3 proteins are 30kD polypeptides with nine closely related members in mammals. They are also found in plants and fungi. 14-3-3 proteins are a family of small. widely expressed. highly conserved cytosolic proteins which bind to and influence the activities of a diverse group of molecules involved in signal transduction. cell cycle regulation and apoptosis. including Raf. PKC. Bad. Cbl. and c-Bcr. Interactions between 14-3-3 and target proteins are strongly influenced by the phosphorylation state of 14-3-3 and the target protein. 14-3-3 proteins form homo- and heterodimeric cup-like structures that bind to discrete phosphoserine-containing motifs. In some instances. 14-3-3 proteins appear to export their binding partners from the nucleus to the cytoplasm in a phosphorylation and Crm1-dependent manner. 14-3-3 sigma shares cyclin-Cdk2 binding motifs with different cell cycle regulators. including p107. p130. p21Cip1. p27Kip1 and p57Kip2 and is associated with cyclin-Cdk complexes in vitro and in vivo. Expression of 14-3-3 sigma is higher in normal epithelial cells.