CDK9 interacts with a RanGTP-Importin-β complex to regulate erythroid enucleation
- Author(s)
- Newton, LM; Lim, KYB; Abeid, DY; Wölwer, CB; Johnson, CJ; Russell, SM; Hawkins, ED; Humbert, PO;
- Abstract
- Erythroid enucleation is the final stage of erythroid terminal differentiation and involves the separation of an orthochromatic erythroblast into two daughter cells; a pyrenocyte containing the extruded nucleus, and a reticulocyte that will become a red blood cell. Our previous work identified CDK9 as a regulator of erythroid enucleation that appears to act independently of its known role in regulating RNA polymerase II transcription, suggesting the potential for a new CDK9 role. Using a co-immunoprecipitation and mass spectrometry approach, we identified the interactome of CDK9 in differentiating erythroblasts. We show that CDK9 interacts with a RanGTP-Importin-β complex during erythroid terminal differentiation, and inhibition of importin-β in erythroblasts blocks erythroid enucleation. Using imaging analysis and functional assays of enucleating erythroblasts, we show that CDK9 and importin-β co-locate at a critical site of activity opposite to the nucleus before nuclear extrusion and we describe a novel finding that physically links CDK9 and importin-β activity prior to CaM/Ca2+ signalling and subsequent F-actin activity to achieve enucleation.
- Keywords
- Cdk9; Enucleation; Erythropoiesis; Importin-β
- Publisher's Version
- https://doi.org/10.1242/jcs.264385
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- Refer to copyright notice on published article.
Creation Date: 2026-03-16 01:38:25
Last Modified: 2026-03-16 01:52:35