PXD052591

PXD052591 is an original dataset announced via ProteomeXchange.

Title	Direct ionic stress sensing and mitigation by the transcription factor NFAT5
Description	Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. To investigate the composition of NFAT5 condensates in response to hypertonic stress, proteins in close proximity of NFAT5 were identified using a variant of NFAT5 fused to TurboID as bait. Hypertonic stress increases NFAT5 proximity to protein complexes belonging to the GO gene sets of “transcription coactivator activity” and “positive regulation of DNA templated transcription initiation.” Closer inspection revealed that the association between NFAT5 and two transcriptional co-activators (the mediator complex and BRD4) and RNAPII itself increased in response to hypertonic stress.
HostingRepository	PRIDE
AnnounceDate	2025-04-17
AnnouncementXML	Submission_2025-04-17_06:36:13.095.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frederic Lamoliatte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-27 07:43:00	ID requested
⏵ 1	2025-04-17 06:36:13	announced

Dataset with its publication pending

submitter keyword: hypertonic stress,proximity biotinylation, biomolecular condensates, ionic stress, intrinsically disordered protein, NFAT5, TonEBP, phase separation

Rajat Rohatgi
contact affiliation	Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
contact email	rrohatgi@stanford.edu
lab head
Frederic Lamoliatte
contact affiliation	University of Dundee
contact email	flamoliatte001@dundee.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD052591

PRIDE project URI

• PRIDE
  1. PXD052591
     1. Label: PRIDE project
     2. Name: Direct ionic stress sensing and mitigation by the transcription factor NFAT5