PXD057905

PXD057905 is an original dataset announced via ProteomeXchange.

Title	ATR-hippo mediates force signalling to nuclear f-actin and links mechanotransduction to neurological disorders.
Description	The mechanical environment is sensed through cell-matrix contacts with the cytoskeleton, but how signals transit the nuclear envelope to impact cell fate decisions remains unknown. Nuclear actin coordinates chromatin motility during differentiation, plasticity and genome maintenance, yet it also remains unclear how nuclear actin responds to mechanical force. Intriguingly, ATR translocates to the nuclear envelope to protect the nucleus during cell motility or compression. Here, we show that ATR drives nuclear actin assembly via recruitment of Filamin-A to the inner nuclear membrane through binding of the hippo pathway scaffold and ATR-substrate, RASSF1A. Moreover, we demonstrate how germline RASSF1 mutation disables nuclear mechanotransduction resulting in cerebral cortex thinning and associates with common psychological traits. Thus, defective mechanical-regulated pathways may provide an explanation for complex neurological disorders.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_04:57:21.538.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-14 10:48:09	ID requested
⏵ 1	2025-05-07 04:57:22	announced

Chatzifrangkeskou M, Stanly T, Koennig D, Campos-Soares L, Eyres M, Hasson A, Perdiou A, Vendrell I, Fischer R, Das S, Gardner S, Go S, Futcher B, Newton A, Skourides P, Szele F, O'Neill E, ATR-hippo drives force signaling to nuclear F-actin and links mechanotransduction to neurological disorders. Sci Adv, 11(7):eadr5683(2025) [pubmed]

10.1126/sciadv.adr5683;

submitter keyword: Human, ATR, RASSF1A, cytoskeleton

Eric O'neill
contact affiliation	Department of Oncology, University of Oxford, OX3 7DQ, UK
contact email	eric.oneill@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	Target Discovery Institute, NDMRB
contact email	iolanda.vendrell@ndm.ox.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/2025/05/PXD057905

PRIDE project URI

• PRIDE
  1. PXD057905
     1. Label: PRIDE project
     2. Name: ATR-hippo mediates force signalling to nuclear f-actin and links mechanotransduction to neurological disorders.