Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor

The mitotic apparatus plays a pivotal role in dividing cells to ensure each daughter cell receives a full set of chromosomes and complement of cytopla sm during mitosis. A human homologue of the Drosophila warts tumor suppress or, h-warts/LATS1, is an evolutionarily conserved serine/threonine kinase a nd a dynamic component of the mitotic apparatus. We have identified an inte raction of h-warts/LATS1 with zyxin, a regulator of actin filament assembly . Zyxin is a component of focal adhesion, however, during mitosis a fractio n of cytoplasmic-dispersed zyxin becomes associated with h-warts/LATS1 on t he mitotic apparatus. We found that zyxin is phosphorylated specifically du ring mitosis, most likely by Cdc2 kinase, and that the phosphorylation regu lates association with h-warts/LATS1. Furthermore, microinjection of trunca ted h-warts/LATS1 protein, including the zyxin-binding portion, interfered with localization of zyxin to mitotic apparatus, and the duration of mitosi s of these injected cells was significantly longer than that of control cel ls. These findings suggest that h-warts/LATS1 and zyxin play a crucial role in controlling mitosis progression by forming a regulatory complex on mito tic apparatus.