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14-3-3 proteins; bringing new definitions to scaffolding

Oncogene volume 20, pages 6331–6338 (2001)Cite this article

Abstract

The 14-3-3 proteins are a part of an emerging family of proteins and protein domains that bind to serine/threonine-phosphorylated residues in a context specific manner, analogous to the Src homology 2 (SH2) and phospho-tyrosine binding (PTB) domains. 14-3-3 proteins bind and regulate key proteins involved in various physiological processes such as intracellular signaling (e.g. Raf, MLK, MEKK, PI-3 kinase, IRS-1), cell cycling (e.g. Cdc25, Wee1, CDK2, centrosome), apoptosis (e.g. BAD, ASK-1) and transcription regulation (e.g. FKHRL1, DAF-16, p53, TAZ, TLX-2, histone deacetylase). In contrast to SH2 and PTB domains, which serve mainly to mediate protein-protein interactions, 14-3-3 proteins in many cases alter the function of the target protein, thus allowing them to serve as direct regulators of their targets. This review focuses on the various mechanisms employed by the 14-3-3 proteins in the regulation of their diverse targets, the structural basis for 14-3-3-target protein interaction with emphasis on the role of 14-3-3 dimerization in target protein binding and regulation and provides an insight on 14-3-3 regulation itself.

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Acknowledgements

We thank Joseph Avruch for helpful discussions during the preparation of the manuscript.

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  1. Division of Molecular Cardiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College of Medicine, Temple, TX 76504, Texas, USA

    Guri Tzivion, Ying H Shen & Jun Zhu

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Correspondence to Guri Tzivion.

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Tzivion, G., Shen, Y. & Zhu, J. 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene 20, 6331–6338 (2001). https://doi.org/10.1038/sj.onc.1204777

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