The 14-3-3 proteins comprise a large family of highly conserved, small, acidic polypeptides of 28-33 kDa 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. The 14-3-3 proteins play a critical role in DNA damage-induced checkpoints by controlling the biological activity of several key cell cycle checkpoint proteins through binding to phosphorylated serine residues. In normal cells, DNA damage leads to activation of cell cycle checkpoints and arrest in the G1 and G2-phases of the cell cycle. 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 a number of different mechanisms. These include inter- and intracompartmental sequestration, activation/inactivation of enzymatic activity and promotion/inhibition of protein interactions.
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