RESUMEN
Signaling via the Akt serine/threonine protein kinase plays critical roles in the self-renewal of embryonic stem cells and their malignant counterpart, embryonal carcinoma cells (ECCs). Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. Furthermore, in ECCs, unphosphorylated Oct4 bound to the AKT1 promoter and repressed its transcription. Phosphorylation of Oct4 by Akt resulted in dissociation of Oct4 from the AKT1 promoter, which activated AKT1 transcription and promoted cell survival. Therefore, a site-specific, posttranslational modification of the Oct4 protein orchestrates the regulation of its stability, subcellular localization, and transcriptional activities, which collectively promotes the survival and tumorigenicity of ECCs.
Asunto(s)
Carcinoma Embrionario/genética , Carcinoma Embrionario/patología , Células Madre de Carcinoma Embrionario/patología , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Secuencia de Aminoácidos , Animales , Apoptosis , Carcinoma Embrionario/metabolismo , Supervivencia Celular , Transformación Celular Neoplásica , Células Madre de Carcinoma Embrionario/metabolismo , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Ratones , Datos de Secuencia Molecular , Factor 3 de Transcripción de Unión a Octámeros/química , Fosforilación , Proteínas Proto-Oncogénicas c-akt/química , Transcripción Genética/genética , Células Tumorales CultivadasRESUMEN
Polymeric dielectrics exhibit remarkable dielectric characteristics and wide applicability, rendering them extensively employed within the domain of electrical insulation. Nevertheless, the electrical strength has always been a bottleneck, preventing its further utilization. Nanocomposite materials can effectively improve insulation strength, but uniform doping of nanofillers in engineering applications is a challenge. Consequently, a nanocomposite interfacial coating was meticulously designed to interpose between the electrode and the polymer, which can significantly improve DC breakdown performance. Subsequently, the effects of filler concentration and coating duration on DC breakdown performance, high field conductivity, and trap distribution characteristics were analyzed. The results indicate that the composite coating introduces deep traps between the electrode-polymer interface, which enhances the carrier confinement, resulting in reduced conductivity and enhanced DC breakdown strength. The incorporation of a composite coating at the interface between the electrode and polymer presents novel avenues for enhancing the dielectric insulation of polymers.