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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\u2013sulfur 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\u2013sulfur cluster delivery independent function of HSCB in erythropoiesis and megakaryopoiesis.<\/jats:p>","DOI":"10.7554\/elife.95815","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T06:25:36Z","timestamp":1710397536000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.95815","source":"Crossref","is-referenced-by-count":4,"title":["PI3K\/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2147-3798","authenticated-orcid":true,"given":"Gang","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rkvz144","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Molecular 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