# The Chromatin Protein CFDP1 Activates TPX2 and Promotes Chromosomal Microtubule Nucleation and Spindle Assembly

## TL;DR

This study shows that the protein CFDP1 is crucial for proper spindle formation during cell division by activating TPX2 and stabilizing microtubules.

## Contribution

The study reveals CFDP1 as a bipartite microtubule-associated protein that activates TPX2 and promotes spindle assembly through importin α dissociation.

## Key findings

- Loss of CFDP1 in mice causes embryonic lethality due to spindle defects and unstable K-fibers.
- CFDP1 promotes Aurora A kinase activation and microtubule nucleation by reducing importin α binding to TPX2.
- CFDP1 has distinct functional domains for nuclear localization and tubulin interaction, aiding spindle assembly.

## Abstract

Microtubule-associated proteins (MAPs) are multifunctional tubulin-binding proteins that contribute to essential aspects of mitotic spindle formation. In the present study, loss of the MAP CFDP1 in mice resulted in gastrulation defects and embryonic lethality at e8.5 due to chromosome segregation spindle defects and loss of K-fiber stability. CFDP1 decreased the association of the nuclear transport protein importin α with the essential spindle assembly factor TPX2, thereby promoting Aurora A kinase activation, microtubule nucleation and spindle assembly. Further defining the CFDP1 mode of action, we identified CFDP1 as a bipartite molecule with an acidic N-terminus that harbors a nuclear localization signal essential for importin α dissociation from TPX2 and a basic C-terminus that interacts with tubulin, co-localizes with the mitotic spindle, and promotes microtubule bundling and polymerization. Together, our studies have established CFDP1 as an essential bipartite MAP involved in chromosomal microtubule nucleation in conjunction with TPX2 and Aurora A while also facilitating nuclear TPX2 activation through importin α dissociation.