CDK9 interacts with a RanGTP-NEMP1-Importin-β complex to regulate erythroid enucleation
Ontology highlight
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-NEMP1-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.
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Erythrocyte, Cell Culture
DISEASE(S): Disease Free
SUBMITTER:
Rohan Lowe
LAB HEAD: Patrick O. Humbert
PROVIDER: PXD072077 | Pride | 2026-04-01
REPOSITORIES: Pride
ACCESS DATA