PXD079708-1

PXD079708 is an original dataset announced via ProteomeXchange.

Title	Taxane-Induced Conformational Changes in the Microtubule Lattice Activate GEF-H1-Dependent RhoA Signaling
Description	Taxanes are widely used chemotherapeutic agents that perturb cell division. They also exert effects during interphase, but the underlying mechanisms are poorly understood. Here, we show that taxanes activate RhoA signaling and induce actin remodeling by displacing the RhoA activator GEF-H1 from microtubules. This taxane-induced release of GEF-H1 occurs rapidly, is independent of tubulin post-translational modifications, and can be recapitulated using purified proteins. In vitro reconstitution assays combined with analyses of microtubule structure revealed that microtubule binding by GEF-H1 is inhibited by microtubule-stabilizing agents that expand the microtubule lattice, such as taxanes and GMPCPP, but not by others, including GTPγS and discodermolide, which stabilize a compacted microtubule lattice. Our findings demonstrate that alterations in microtubule lattice conformation can activate key signaling pathways, offering new insights into the mode of action of taxanes and the possible origins of their side effects.
HostingRepository	PRIDE
AnnounceDate	2026-08-20
AnnouncementXML	Submission_2026-08-20_04:08:24.258.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marèl Spoelstra
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-15 06:48:15	ID requested
⏵ 1	2026-08-20 04:08:24	announced

Dataset with its publication pending

submitter keyword: RhoA Signaling,GEF-H1, microtubules

Anna Akhmanova
contact affiliation	Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan, Utrecht, 3584 CS, The Netherlands
contact email	a.akhmanova@uu.nl
lab head
Marèl Spoelstra
contact affiliation	Utrecht University
contact email	m.f.m.spoelstra@uu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD079708
     1. Label: PRIDE project
     2. Name: Taxane-Induced Conformational Changes in the Microtubule Lattice Activate GEF-H1-Dependent RhoA Signaling