Rnd3/RhoE expression is regulated by G-actin through MKL1-SRF signaling pathway.

Autor: Piquet L; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Robbe T; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Neaud V; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Basbous S; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Rosciglione S; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Saltel F; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France., Moreau V; INSERM, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France; Univ. Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France. Electronic address: violaine.moreau@inserm.fr.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2018 Sep 15; Vol. 370 (2), pp. 227-236. Date of Electronic Publication: 2018 Jun 22.
DOI: 10.1016/j.yexcr.2018.06.023
Abstrakt: Rnd3/RhoE is an atypical member of the Rho family of small GTPases, devoid of intrinsic GTP hydrolytic activity and a general modulator of important cellular processes such as migration and proliferation. Here, we show that Rnd3 is a target of the transcription factor SRF and its co-activator MKL1. The MKL1-SRF pathway assures the translation of physical forces into a transcriptional response. Rho GTPases can modulate the activity of this mechanotransduction pathway through actin cytoskeleton regulation, and many MKL1-SRF targets are involved in the regulation of actin. We found that Rnd3 expression is altered by G-actin signaling and sensitive to actin-targeting drugs and MKL1 mutants. We further characterized a consensus SRF binding site in the Rnd3 promoter. We found that MKL1-SRF modulation regulates Rnd3 promoter activity and Rnd3 expression can affect MKL1-SRF pathway activity in return. We demonstrated that this novel MKL1-SRF target is required in mechanosensitive mechanisms such as cell spreading and spheroid formation. Thus, Rnd3 is a MKL1-SRF target that plays a key role in the feedback loop described between the MKL1-SRF pathway and the organization of the actin cytoskeleton.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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