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- W2901681617 abstract "MRTF-A (myocardin-related transcription factor A) is a coactivator for SRF-mediated gene expression. The activity of MRTF-A is critically dependent on the dissociation of G-actin from N-terminal RPEL motifs. MRTF-SRF induction often correlates with enhanced polymerization of F-actin. Here we investigate MRTF regulation by the multifunctional JMY protein, which contains three WASP/verprolin homology 2 (WH2/V) domains and facilitates Arp2/3-dependent and -independent actin nucleation.Co-immunoprecipitation experiments, immunofluorescence and luciferase reporter assays were combined with selective inhibitors to investigate the effect of JMY and its domains on MRTF-A in NIH 3 T3 mouse fibroblasts.JMY induced MRTF-A transcriptional activity and enhanced its nuclear translocation. Unexpectedly, MRTF-A was hyperactivated when the Arp2/3-recruiting CA region of JMY was deleted or mutated, suggesting an autoinhibitory mechanism for full-length JMY. Moreover, isolated WH2/V domains which are unable to nucleate actin were sufficient for nuclear accumulation and SRF activation. Recombinant WH2/V regions of JMY biochemically competed with MRTF-A for actin binding. Activation of MRTF-A by JMY was unaffected by Arp3 knockdown, by an Arp2/3 inhibitor, and by latrunculin which disassembles cellular F-actin. Restriction of JMY to the nucleus abrogated its MRTF-A activation. Finally, JMY RNAi reduced basal and stimulated transcriptional activation via MRTF-A.Our results suggest that JMY activates MRTF-SRF independently of F-actin via WH2/V-mediated competition with the RPEL region for G-actin binding in the cytoplasm. Furthermore, the C-terminal region facilitates an autoinhibitory effect on full-length JMY, possibly by intramolecular folding." @default.
- W2901681617 created "2018-11-29" @default.
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- W2901681617 date "2018-11-21" @default.
- W2901681617 modified "2023-10-18" @default.
- W2901681617 title "Regulation of MRTF-A by JMY via a nucleation-independent mechanism" @default.
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- W2901681617 doi "https://doi.org/10.1186/s12964-018-0299-x" @default.
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