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RASSF1A IS REQUIRED FOR THE MAINTENANCE OF NUCLEAR ACTIN LEVELS

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: iolanda Vendrell

LAB HEAD: Eric O'Neil

PROVIDER: PXD011517 | Pride | 2019-05-30

REPOSITORIES: Pride

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			Action	DRS
	1_MST2_untr_1_F307741.xml	Xml
	5_MST2_untr_2_F307742.xml	Xml
	9_MST2_Untr_3_F307744.xml	Xml
	QE660_MSQ708_DafniPefani_20160805_1_MST2_Untr_1_1ul.mgf	Mgf
	QE660_MSQ708_DafniPefani_20160805_1_MST2_Untr_1_1ul.raw	Raw

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