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A central chaperone-like role for 14-3-3 proteins in human cells
Dmitri Segal1, Stefan Maier2, Giovanni J Mastromarco3
1Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
Molecular Cell
|March 17, 2023
Summary
14-3-3 proteins act as molecular chaperones, preventing client protein aggregation. This study maps their interactions, revealing a key role in regulating protein localization and function, particularly for RNA-binding proteins.
Area of Science:
- Cellular Biology
- Molecular Biology
- Protein Interactions
Background:
- 14-3-3 proteins are crucial regulators in cellular signaling networks.
- Their specific roles and paralog differences in client protein regulation remain largely uncharacterized.
Purpose of the Study:
- To comprehensively map the interactomes of all human 14-3-3 protein paralogs.
- To investigate the functional consequences of disrupting 14-3-3 interactions on client protein localization and behavior.
Main Methods:
- Interactome mapping of all human 14-3-3 paralogs.
- Systematic characterization of client protein localization upon disruption of 14-3-3 binding.
- Functional analysis of RNA-binding protein SAMD4A regulation by 14-3-3 proteins.
Main Results:
- Loss of 14-3-3 binding causes client proteins to form discrete foci in a client-specific manner.
- 14-3-3 binding motifs can suppress aggregation and phase separation of nonclient proteins.
- 14-3-3 proteins inhibit the RNA-binding protein SAMD4A's cytoplasmic localization and translational repressor activity.
Conclusions:
- 14-3-3 proteins possess a significant chaperone-like function, maintaining client protein solubility and localization.
- These findings expand the known roles of 14-3-3 proteins beyond signaling hubs to include protein quality control.
Keywords:
14-3-3 proteinsaffinity purificationaggregationchaperonesfunctional proteomicsmass spectrometryphase transitionsprotein quality controlproximity-dependent biotinylationMore Related Videos
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