The 14-3-3 proteins comprise a large family of highly conserved, small, acidic polypeptides that are found in all eukaryotic species and play important roles in a wide range of cellular processes including signal transduction, apoptosis, cell cycle progression and checkpoint activation. In humans, seven different genes encode the highly conserved 14-3-3 isotypes (α, β, γ, δ, ε, η, σ, τ, and ζ). The 14-3-3 proteins regulate numerous cellular signaling circuits that are implicated in cancer development. They bind to protein ligands following their serine/threonine phosphorylation at a defined motif and regulate their activities by different mechanisms. These include inter- and intra-compartmental sequestration, activation/inactivation of enzymatic activity and promotion/inhibition of protein interactions...