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FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning



Date Posted : July 24, 2019

Posted by EMBO Rep (2019)e47495 in : Michael Cuccione Childhood Cancer Research Program
Source: EMBP Press


The concerted action of many protein kinases helps orchestrate the error‐free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin‐dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1α, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle positioning and timely cell division. CK1α is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1α‐binding‐deficient FAM83DF283A/F283A knockin mutations, display pronounced spindle positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D−/− cells, or artificially delivering CK1α to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1α as new mitotic kinase that orchestrates the kinetics and orientation of cell division.

Chldhood Cancer Research

The prominent mitotic roles for kinases such as cyclin‐dependent kinases (CDKs), Aurora kinases, Polo‐like kinases (PLKs) and Nima‐related kinases (NEKs) have been well characterised 1-7. However, the role of Casein Kinase 1 alpha (CK1α) in mitosis, if any, remains poorly defined. CK1α belongs to the CK1 family of Ser/Thr protein kinases that are implicated in diverse roles in a whole plethora of cellular processes, from Wnt signalling to the regulation of circadian rhythms 8. CK1 isoforms can phosphorylate hundreds of proteins in vitro, with a preference for Ser/Thr residues that conform to either a D/E‐X‐X‐S*/T* or pS/pT‐X‐X‐S*/T* motif 9.

A recent mitotic phosphoproteomic study found that around half of the identified phosphorylation sites conformed to the predicted CK1‐consensus phosphorylation motifs 10, potentially implying a significant role for CK1 catalytic activity in mitotic protein phosphorylation. Yet, there is a lack of definitive evidence regarding whether and how any of the CK1 isoforms, or CK1α in particular, are involved in mitosis.

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