Unlocking the code of 14-3-3.
One of the most striking 'rags to riches' stories in the protein world is that of 14-3-3, originally identified in 1967 as merely an abundant brain protein. The first clues that 14-3-3 would play an important role in cell biology came almost 25 years later when it was found to interact with various proto-oncogene proteins and signaling proteins. The subsequent identification of 14-3-3 as a phosphoserine/phosphothreonine-binding protein firmly established its importance in cell signaling. 14-3-3 family members are found in all eukaryotes - from plants to mammals - and more than 100 binding partners have been identified to date. The targets of 14-3-3 are found in all subcellular compartments and their functional diversity is overwhelming - they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors. 14-3-3 binding can alter the localization, stability, phosphorylation state, activity and/or molecular interactions of a target protein. Recent studies now indicate that the serine/threonine protein phosphatases PP1 and PP2A are important regulators of 14-3-3 binding interactions, and demonstrate a role for 14-3-3 in controlling the translocation of certain proteins from the cytoplasmic and endoplasmic reticulum to the plasma membrane. New reports also link 14-3-3 to several neoplastic and neurological disorders, where it might contribute to the pathogenesis and progression of these diseases.
Dougherty
Michele K
MK
Laboratory of Protein Dynamics and Signaling, NCI-Frederick, Frederick, MD 21702, USA.
Morrison
Deborah K
DK
D048948:14-3-3 Proteins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010940:Plant Proteins / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction
D048948:14-3-3 Proteins; C000715470:MAS1 protein, human; D010940:Plant Proteins; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D010749:Phosphoprotein Phosphatases