PXD027268

PXD027268 is an original dataset announced via ProteomeXchange.

Title	Nuclear-capture of endosomes drives depletion of nuclear G-actin to promote SRF/MRTF gene expression and cancer cell invasiveness (part 2: Surface and Nuclear Proteomes)
Description	Signals are relayed from receptor tyrosine kinases (RTKs) at the cell surface to effector systems in the cytoplasm and nucleus, and coordination of this process is important for the execution of migratory phenotypes, such as cell scattering and invasion. The endosomal system influences how RTK signalling is coded, but the ways in which it transmits these signals to the nucleus to influence gene expression are not yet clear. Here we show that an RTK, MET promotes Rab17- and clathrin-dependent endocytosis of EphA2, another RTK, followed by centripetal transport of EphA2-positive endosomes. EphA2 then mediates physical capture of endosomes on the outer surface of the nucleus; a process involving interaction between the nuclear import machinery and a nuclear localisation sequence in EphA2’s cytodomain. Nuclear capture of EphA2 promotes RhoG-dependent phosphorylation of the actin-binding protein, cofilin to oppose nuclear import of G-actin. The resulting depletion of nuclear G-actin drives transcription of Myocardin-related transcription factor (MRTF)/serum-response factor (SRF)-target genes to implement cell scattering and the invasive behaviour of cancer cells.
HostingRepository	PRIDE
AnnounceDate	2023-04-11
AnnouncementXML	Submission_2023-04-11_06:11:08.811.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SergioLilla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	isotope labeled residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-13 05:16:02	ID requested
1	2021-09-28 04:07:17	announced
⏵ 2	2023-04-11 06:11:11	announced	2023-04-11: Updated project metadata.

Marco S, Neilson M, Moore M, Perez-Garcia A, Hall H, Mitchell L, Lilla S, Blanco GR, Hedley A, Zanivan S, Norman JC, Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion. Nat Commun, 12(1):6829(2021) [pubmed]

submitter keyword: invasiveness, Serum-response factor (SRF), cell:cell repulsion, EphA2, Heptocyte growth factor (HGF), Rab17, surface and nuclear proteome, actin polymerisation, Myocardin-related transcription factor (MRTF),nuclear G-actin, nuclear import, pancreatic adenocarcinoma (PDAC)

Sara RossanaZanivan
contact affiliation	CRUK - Beatson Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.zanivan@beatson.gla.ac.uk
lab head
SergioLilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.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/2021/09/PXD027268

PRIDE project URI

• PRIDE
  1. PXD027268
     1. Label: PRIDE project
     2. Name: Nuclear-capture of endosomes drives depletion of nuclear G-actin to promote SRF/MRTF gene expression and cancer cell invasiveness (part 2: Surface and Nuclear Proteomes)