PXD027268 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
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) |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027268
- Label: PRIDE project
- 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)