# Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle

## TL;DR

This paper reveals how the proteins Nek2 and Kif24 work together to break down cell structures called cilia before cells divide, and how this process is linked to cancer cell growth.

## Contribution

The study identifies Kif24 as a new physiological substrate of Nek2, revealing a novel mechanism for cilium disassembly during the cell cycle.

## Key findings

- Nek2 phosphorylates Kif24, enhancing its activity to prevent cilia formation.
- Nek2 and Kif24 promote cilium disassembly independently of Aurora A and HDAC6.
- Overexpression of Nek2 and Kif24 in breast cancer cells reduces ciliation and proliferation.

## Abstract

Many proteins are known to promote ciliogenesis, but mechanisms that promote primary cilia disassembly prior to mitosis are largely unknown. Here, we identify a mechanism that favors cilium disassembly and maintains the disassembled state. We show that co-localization of the S/G2 phase kinase, Nek2, and Kif24 triggers Kif24 phosphorylation, inhibiting cilia formation. We show that Kif24, a microtubule depolymerizing kinesin, is phosphorylated by Nek2, which stimulates its activity and prevents the outgrowth of cilia in proliferating cells, independent of Aurora A and HDAC6. Our data also suggest that cilium assembly and disassembly are in dynamic equilibrium, but Nek2 and Kif24 can shift the balance toward disassembly. Further, Nek2 and Kif24 are over-expressed in breast cancer cells, and ablation of these proteins restores ciliation in these cells, thereby reducing proliferation. Thus, Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule de-polymerization.