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Signal transduction events can be regulated both by posttranslational modifications and by protein-protein interactions. 14-3-3 proteins are critically involved in both of these processes. The 14-3-3s, originally catalogued as small, abundant brain proteins, are expressed as multiple isoforms in all eukaryotic cells and are now known to recognize and to bind to distinct phosphoserine or phosphothreonine motifs on target proteins. Their binding partners include key proteins involved in metabolism, cell cycle control, the DNA damage response, transcription, protein synthesis, and apoptosis. This STKE Review with 2 figures and 127 references describes 14-3-3 proteins and highlights how these simple proteins have profound effects on the regulation of a vast number of cellular events.
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