PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis

• DOI: 10.7554/elife.95815.1
• Publication Date: 2024-03-14T10:25:20Z
• Authors: Gang Liu; Yunxuan Hou; Xin Jin; Yixue Zhang; Chaoyue Sun; Chengquan Huang; Yujie Ren; Jianmin Gao; Xiuli Wang; Xiumei Jiang
• Keywords: HSCB; 0301 basic medicine; QH301-705.5; Science; Active Transport, Cell Nucleus; FOG1 nuclear translocation; PI3K; Thrombopoiesis; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Humans; Erythropoiesis; Biology (General); Cell Nucleus; Q; R; HSC70 Heat-Shock Proteins; Nuclear Proteins; Cell Biology; Hematopoietic Stem Cells; Protein Transport; Medicine; K562 Cells; megakaryopoiesis; erythropoiesis; Transcription Factors; Signal Transduction

Erythropoiesis and megakaryopoiesis are stringently regulated by signaling pathways. However, the precise molecular mechanisms through which pathways regulate key transcription factors controlling erythropoiesis remain partially understood. Herein, we identified heat shock cognate B (HSCB), is well known for its iron-sulfur cluster delivery function, as an indispensable protein friend of GATA 1 (FOG1) nuclear translocation during K562 human erythroleukemia cells cord-blood-derived CD34+CD90+ hematopoietic stem (HSCs), HSCs. Mechanistically, HSCB could be phosphorylated phosphoinositol-3-kinase (PI3K) to bind with mediate proteasomal degradation transforming acidic coiled-coil containing 3 (TACC3), otherwise detained FOG1 in cytoplasm, thereby facilitating translocation. Given that PI3K activated both megakaryopoiesis, a factor these processes, our findings elucidate important, previously unrecognized independent function megakaryopoiesis.