PXD011517

PXD011517 is an original dataset announced via ProteomeXchange.

Title	RASSF1A IS REQUIRED FOR THE MAINTENANCE OF NUCLEAR ACTIN LEVELS
Description	Nuclear actin participates in many essential cellular processes including gene transcription, chromatic remodelling and mRNA processing. Actin shuttles into and out the nucleus through the action of dedicated transport receptors importin-9 and exportin-6, but how this transport is regulated remains unclear. Here we show that RASSF1A is a novel regulator of actin nucleocytoplasmic trafficking and is required for the active maintenance of nuclear actin levels through supporting binding of exportin-6 (XPO6) to RAN GTPase. RASSF1A (Ras association domain family 1 isoform A) is a tumor suppressor gene frequently silenced by promoter hypermethylation in all major solid cancers. Specifically, we demonstrate that endogenous RASSF1A localizes to the nuclear envelope (NE) and is required for nucleo-cytoplasmic actin transport and the concomitant regulation of Myocardin-related transcription factor A (MRTF-A), a coactivator of the transcription factor serum response factor (SRF). The RASSF1A/RAN/XPO6/nuclear actin pathway is aberrant in cancer cells where RASSF1A expression is lost and correlates with reduced MTRF/SRF activity leading to cell adhesion defects. Taken together, we have identified a previously unknown mechanism by which the nuclear actin pool is regulated and uncovered a previously unknown link of RASSF1A and MTRF/SRF in tumor suppression.
HostingRepository	PRIDE
AnnounceDate	2019-05-30
AnnouncementXML	Submission_2019-06-14_00:30:50.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	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-30 02:37:16	ID requested
1	2019-05-30 08:33:01	announced
⏵ 2	2019-06-14 00:30:51	announced	Updated publication reference for PubMed record(s): 31175105.

curator keyword: Biological

submitter keyword: RASSF1A, MST2, nuclear envelope, nuclear actin, nucleocytoplasmic shuttling, nuclear export, exportin-6, SRF, MRTF-A

Eric O'Neil
contact affiliation	Department of Oncology, University of Oxford, Oxford, Oxfordshire, OX3 7DQ, UK
contact email	eric.oneill@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	CRUK-MRC Oxford Institute for Radiation Oncology, Oxford University
contact email	iolanda.vendrell@oncology.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011517
     1. Label: PRIDE project
     2. Name: RASSF1A IS REQUIRED FOR THE MAINTENANCE OF NUCLEAR ACTIN LEVELS