We report that Yap1 is dispensable for the maintenance of ES cells while Yap1 is required for the differentiation of ES cells using global gene expression profile Overall design: RNA-seq analysis upon KD of Yap1 in ES and differentiated ES cells and overexpression of Yap1
Yap1 is dispensable for self-renewal but required for proper differentiation of mouse embryonic stem (ES) cells.
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View SamplesReduced eukaryotic Initiation Factor 2 (eIF2)a phosphorylation (p-eIF2a) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2a has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2a in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2a in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ?FosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2a and the gateway drug properties of psychoactive cannabinoids. Overall design: RNAseq from PC12 cell line with a 6 hour DMSO or WIN treatment.
Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.
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