14-3-3 is a class of proteins able to interact with a multitude of targets by establishing
protein-protein interactions (PPIs). They are usually found in all eukaryotes
with a conserved secondary structure and high sequence homology among species. 14-3-3
proteins are involved in many physiological and pathological cellular processes either by
triggering or interfering with the activity of specific protein partners. In the last years, the
scientific community has collected many evidences on the role played by seven human
14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate
the molecular mechanisms associated to these diseases by interacting with (i) oncogenic
and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer
diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate
complete understanding of the physiological role of these proteins, and might offer valuable
therapeutic approaches for these critical pathological states.
Keywords: 14-3-3, cancer, neurodegeneration, protein-protein interaction, small molecules, drug discovery, phosphorylation.
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