14‐3‐3 Proteins

Abstract

The 14‐3‐3 proteins are a family of multifunctional regulators in eukaryotic organisms. Through binding to over 200 client proteins, 14‐3‐3 proteins regulate numerous cellular functions, which include metabolic pathways, molecular trafficking, and cell‐cycle progression. Most 14‐3‐3 interactions are mediated by defined phosphoserine/threonine motifs within the target protein sequence. The presence of these phosphorylated motifs allows for integration of 14‐3‐3 interactions with client proteins into a diverse cellular signaling network, through the actions of various protein kinases and phosphatases. As evidence of its vital role in cell function, 14‐3‐3 has been implicated in human diseases, such as cancer and neuronal disorders. Thus, development of small‐molecule 14‐3‐3 modulators will allow the continued discovery of the critical importance of 14‐3‐3 in normal physiology and lead to future use as targeted therapies in human disease.