PXD063348

PXD063348 is an original dataset announced via ProteomeXchange.

Title	Transcriptional adaptation after deletion of Cdc42 in primary T cells
Description	Cdc42 is a Rho family GTPase known for its central role in cell polarity and cytoskeletal regulation. To understand the role of Cdc42 in polarised secretion from cytotoxic T lymphocytes (CTLs) we used CRISPR/Cas9 gene deletion. While Cdc42-deleted CTLs initially showed reduced secretion for up to two days after CRISPR-mediated deletion, full secretion was rapidly restored and even enhanced while CDC42 protein remained absent. In contrast, chemical inhibition of CDC42 using CASIN consistently decreased secretion in wild-type cells, but had no impact on Cdc42-deleted CTLs, confirming the specificity of this inhibitor. Comparative proteomics and transcriptomics of CTLs after Cdc42-deletion revealed transcriptional changes that could support improved T cell function including compensation via other Rho GTPases. Targeting the promoter region of Cdc42 did not trigger transcriptional adaptation, consistent with a nonsense-mediated decay mechanism of genetic compensation. Our work highlights the importance of taking orthogonal approaches to study protein function, and reveals the remarkable robustness of primary T cells to adapt to loss of an essential gene.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_18:03:16.765.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Rollings
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-25 10:23:40	ID requested
⏵ 1	2025-09-07 18:03:17	announced

Rochussen AM, Ma CY, Griffiths GM, Transcriptional adaptation after deletion of Cdc42 in primary T cells. J Cell Sci, 138(15):(2025) [pubmed]

10.1242/jcs.263826;

submitter keyword: T cell, Rho GTPase, CRISPR/Cas9,Transcriptional adaptation, CDC42

Professor Gillian Griffiths
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge, UK
contact email	gg305@cam.ac.uk
lab head
Christina Rollings
contact affiliation	University of Dundee
contact email	crollings@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063348
     1. Label: PRIDE project
     2. Name: Transcriptional adaptation after deletion of Cdc42 in primary T cells