Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation

Tanaya Roychowdhury, Seth W. McNutt, Chiranjeevi Pasala, Hieu T. Nguyen, Daniel T. Thornton, Sahil Sharma, Luke Botticelli, Chander S. Digwal, Suhasini Joshi, Nan Yang, Palak Panchal, Souparna Chakrabarty, Sadik Bay, Vladimir Markov, Charlene Kwong, Jeanine Lisanti, Sun Young Chung, Stephen D. Ginsberg, Pengrong Yan, Elisa Stanchina, Adriana Corben, Shanu Modi, Mary L. Alpaugh, Giorgio Colombo, Hediye Erdjument-Bromage, Thomas A. Neubert, Robert J. Chalkley, Peter R. Baker, Alma L. Burlingame, Anna Rodina, Gabriela Chiosis () and Feixia Chu ()
Additional contact information
Tanaya Roychowdhury: Memorial Sloan Kettering Cancer Center
Seth W. McNutt: University of New Hampshire
Chiranjeevi Pasala: Memorial Sloan Kettering Cancer Center
Hieu T. Nguyen: University of New Hampshire
Daniel T. Thornton: University of New Hampshire
Sahil Sharma: Memorial Sloan Kettering Cancer Center
Luke Botticelli: University of New Hampshire
Chander S. Digwal: Memorial Sloan Kettering Cancer Center
Suhasini Joshi: Memorial Sloan Kettering Cancer Center
Nan Yang: University of New Hampshire
Palak Panchal: Memorial Sloan Kettering Cancer Center
Souparna Chakrabarty: Memorial Sloan Kettering Cancer Center
Sadik Bay: Memorial Sloan Kettering Cancer Center
Vladimir Markov: Memorial Sloan Kettering Cancer Center
Charlene Kwong: Memorial Sloan Kettering Cancer Center
Jeanine Lisanti: Memorial Sloan Kettering Cancer Center
Sun Young Chung: Memorial Sloan Kettering Cancer Center
Stephen D. Ginsberg: NYU Grossman School of Medicine
Pengrong Yan: Memorial Sloan Kettering Cancer Center
Elisa Stanchina: Memorial Sloan Kettering Cancer Center
Adriana Corben: Memorial Sloan Kettering Cancer Center
Shanu Modi: Memorial Sloan Kettering Cancer Center
Mary L. Alpaugh: Memorial Sloan Kettering Cancer Center
Giorgio Colombo: University of Pavia
Hediye Erdjument-Bromage: NYU Grossman School of Medicine
Thomas A. Neubert: NYU Grossman School of Medicine
Robert J. Chalkley: University of California
Peter R. Baker: University of California
Alma L. Burlingame: University of California
Anna Rodina: Memorial Sloan Kettering Cancer Center
Gabriela Chiosis: Memorial Sloan Kettering Cancer Center
Feixia Chu: University of New Hampshire

Nature Communications, 2024, vol. 15, issue 1, 1-28

Abstract: Abstract The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90’s interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53178-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53178-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53178-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().