@article{afbc63cd84a74ca686be8a84980ec413,
title = "A central chaperone-like role for 14-3-3 proteins in human cells",
abstract = "14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients and act as central hubs of signaling networks. However, how 14-3-3 paralogs differ in specificity and how they regulate client protein function are not known for most clients. Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. The loss of 14-3-3 binding leads to the coalescence of a large fraction of clients into discrete foci in a client-specific manner, suggesting a central chaperone-like function for 14-3-3 proteins. Congruently, the engraftment of 14-3-3 binding motifs to nonclients can suppress their aggregation or phase separation. Finally, we show that 14-3-3s negatively regulate the localization of the RNA-binding protein SAMD4A to cytoplasmic granules and inhibit its activity as a translational repressor. Our work suggests that 14-3-3s have a more prominent role as chaperone-like molecules than previously thought.",
keywords = "14-3-3 proteins, affinity purification, aggregation, chaperones, functional proteomics, mass spectrometry, phase transitions, protein quality control, proximity-dependent biotinylation",
author = "Dmitri Segal and Stefan Maier and Mastromarco, {Giovanni J.} and Qian, {Wesley Wei} and Syed Nabeel-Shah and Hyunmin Lee and Gaelen Moore and Jessica Lacoste and Brett Larsen and Lin, {Zhen Yuan} and Abeeshan Selvabaskaran and Karen Liu and Craig Smibert and Zhaolei Zhang and Jack Greenblatt and Jian Peng and Lee, {Hyun O.} and Gingras, {Anne Claude} and Mikko Taipale",
note = "Funding Information: We thank Dr. Howard Lipshitz and Timothy Low for fruitful discussions during the project, Nujhat Ahmed for technical assistance in iCLIP experiments, and Nader Alerasool for assistance with RNA-seq data processing. This work was supported by an NSERC Discovery grant ( 5006347 ) to M.T., a CIHR Foundation grant to J.G. ( FDN154338 ), a CIHR Foundation grant to A.-C.G. ( FDN143301 ), and a Canada Foundation for Innovation John R. Evans Leaders Fund grant to M.T. Salary support included a Canada Research Chair (Tier 2) in functional proteomics and proteostasis for M.T., a Canada Research Chair (Tier 1) in functional proteomics to A.-C.G., an NSERC Postgraduate Scholarship —doctoral for D.S., and an NSERC Canada Graduate Scholarship —doctoral for H.L. proteomics work was performed at the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by Canada Foundation for Innovation funding, by the Government of Ontario and by Genome Canada and Ontario Genomics ( OGI-139). Sequencing was performed at the Donnelly Sequencing Centre. Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = mar,
day = "16",
doi = "10.1016/j.molcel.2023.02.018",
language = "English (US)",
volume = "83",
pages = "974--993.e15",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}