CDK9 interacts with a RanGTP-importin-beta complex to regulate erythroid enucleation

Newton, LM; Lim, KYB; Abeid, DY; Johnson, CJ; Russell, SM; Hawkins, ED; Humbert, PO

Author(s): Newton, LM; Lim, KYB; Abeid, DY; Johnson, CJ; Russell, SM; Hawkins, ED; Humbert, PO;
Details: Publication Year 2026-06-15,Volume 139,Issue #12,Page jcs264385
Journal Title: Journal of Cell Science
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, which will become a red blood cell. Our previous work has 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 here identified the interactome of CDK9 in differentiating erythroblasts. We show that CDK9 interacts with a RanGTP-importin-beta complex during erythroid terminal differentiation, and inhibition of importin-beta in erythroblasts blocks erythroid enucleation. Using imaging analysis and functional assays of enucleating erythroblasts, we show that CDK9 and importin-beta colocate at a crucial site of activity opposite to the nucleus before nuclear extrusion and we describe a novel finding that physically links CDK9 and importin-beta activity prior to calmodulin and Ca2+ signalling, and subsequent F-actin activity, to achieve enucleation.
Publisher: COB
Keywords: *Cyclin-Dependent Kinase 9/metabolism/genetics; *beta Karyopherins/metabolism/genetics; Animals; Humans; *Cell Nucleus/metabolism; *ran GTP-Binding Protein/metabolism; Mice; *Erythroblasts/metabolism/cytology; Cell Differentiation; Protein Binding; Actins/metabolism; Cdk9; Enucleation; Erythropoiesis; Importin-beta
Research Division(s): Inflammation
PubMed ID: 41716140
Publisher's Version: https://doi.org/10.1242/jcs.264385
Open Access at Publisher's Site: https://doi.org/10.1242/jcs.264385
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-16 01:38:25

Last Modified: 2026-04-27 03:54:31