RESUMO
Erythropoiesis and megakaryopoiesis are stringently regulated by signaling pathways. However, the precise molecular mechanisms through which signaling pathways regulate key transcription factors controlling erythropoiesis and megakaryopoiesis remain partially understood. Herein, we identified heat shock cognate B (HSCB), which is well known for its iron-sulfur cluster delivery function, as an indispensable protein for friend of GATA 1 (FOG1) nuclear translocation during erythropoiesis of K562 human erythroleukemia cells and cord-blood-derived human CD34+CD90+hematopoietic stem cells (HSCs), as well as during megakaryopoiesis of the CD34+CD90+HSCs. Mechanistically, HSCB could be phosphorylated by phosphoinositol-3-kinase (PI3K) to bind with and mediate the proteasomal degradation of transforming acidic coiled-coil containing protein 3 (TACC3), which otherwise detained FOG1 in the cytoplasm, thereby facilitating FOG1 nuclear translocation. Given that PI3K is activated during both erythropoiesis and megakaryopoiesis, and that FOG1 is a key transcription factor for these processes, our findings elucidate an important, previously unrecognized iron-sulfur cluster delivery independent function of HSCB in erythropoiesis and megakaryopoiesis.
Assuntos
Eritropoese , Fosfatidilinositol 3-Quinases , Fatores de Transcrição , Humanos , Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , Eritropoese/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Choque Térmico HSC70/metabolismo , Células K562 , Proteínas Nucleares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transporte Proteico , Transdução de Sinais , Trombopoese/fisiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
The paper capillary is introduced to enable effective sampling on microfluidic paper analytical devices. By coupling the macroscale capillary force of paper capillary and the microscale capillary forces of native paper, fluid transport can be flexibly tailored with proper design. Subsequently, a hybrid-fluid-mode paper capillary device was proposed which enables fast and reliable sampling in an arrayed form with less surface adsorption and bias for different components. The resulting device thus supports high-throughput, quantitative, and repeatable assays by manual operation. With all these merits, multiplex analysis of ions, proteins, and microbes have all been realized on this platform, which has paved the way to higher analysis on µPADs.