Here we show that Eplin-alpha transcription is regulated by actin-MAL-SRF signalling. Upon signal induction, the coactivator MAL/MRTF is released from a repressive complex with monomeric actin, binds the transcription factor SRF and activates target gene expression. In a transcriptome analysis with a combination of actin binding drugs which specifically and differentially interfere with the actin-MAL complex
(Descot et al., 2009), we Ferroptosis mutation identified Eplin to be primarily controlled by monomeric actin. Further analysis revealed that induction of the Eplin-alpha mRNA and its promoter was sensitive to drugs and mutant actins which stabilise the repressive actin-MAL complex. In contrast, the Eplin-beta isoform remained unaffected. Knockdown of MRTFs or dominant negative MAL which inhibits SRF-mediated transcription impaired Eplin-alpha expression. Conversely, constitutively active mutant actins and MAL induced Eplin-alpha. MAL and SRF were bound to a consensus SRF binding site of the Eplin-alpha promoter; the recruitment of MAL to this region was enhanced sever-alfold upon induction. The tumor suppressor Eplin-alpha is thus a novel cytoskeletal Daporinad inhibitor target gene transcriptionally regulated by the actin-MAL-SRF pathway, which supports a role in cancer biology.”
“In a previous study, we reported a dissociation between subjective expectancy and motor behaviour in a simple associative
learning task (Perruchet, Cleeremans, Destrebecqz, 2006). According
to previous conditioning studies (Clark, Manns, Squire, 2001), this dissociation GNS-1480 is observed when the to-be-associated events coterminate and thus overlap in time (a training regimen called delay conditioning), but not when they are separated by a temporal delay (trace conditioning). In this latter situation indeed, there tends to be a direct relationship between subjective expectancy and behaviour. In this study, we further investigated this issue in a series of experiments where conscious and unconscious components of performance were pitted against each other. In Experiments 1-3, participants performed a simple reaction time task in which a preparatory signal (a tone) either overlapped with or terminated earlier than the imperative stimulus (a visual target presented in 50% of the trials). After each response, participants also had to state how much they expected the imperative stimulus to be displayed on the next trial. Results indicate that reaction times tend to decrease when the tone is consistently followed by the visual target across successive trials, whereas conscious expectancy for the target decreases at the same time. Importantly, we systematically found that the temporal relationship between the tone and the target failed to influence performance. In a fourth experiment, we examined whether these results extend to a two-choice reaction time task.