Cyclin-dependent Kinase 1 and Aurora Kinase choreograph mitotic storage and redistribution of a growth factor receptor.
Christina D CotaMatthew S DreierWilliam N ColganAnna ChaTwan SiaBrad DavidsonPublished in: PLoS biology (2021)
Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppressing endosomal degradation and recycling pathways. As cells progress through metaphase, loss of CDK1 activity permits differential degradation and targeted recycling of stored receptors, leading to asymmetric induction. Mitotic receptor storage, as delineated in this study, may facilitate rapid reestablishment of signaling competence in nascent daughter cells. However, mutations that limit or enhance the release of stored signaling components could alter daughter cell fate or behavior thereby promoting oncogenesis.
Keyphrases
- cell cycle
- cell cycle arrest
- growth factor
- induced apoptosis
- protein kinase
- cell proliferation
- tyrosine kinase
- cell fate
- cell death
- single cell
- cancer therapy
- room temperature
- pi k akt
- genome wide
- drug delivery
- cell therapy
- oxidative stress
- signaling pathway
- stem cells
- gene expression
- mesenchymal stem cells
- binding protein
- ionic liquid