Autoinhibition and relief mechanism for Polo-like kinase 4

1. 1. Joseph E. Klebbaa,
   2. Daniel W. Bustera,
   3. Tiffany A. McLamarraha,
   4. Nasser M. Rusanb, and
   5. Gregory C. Rogersa,1

Polo-like kinases (Plks) are a conserved family of enzymes that function as master regulators for the process of cell division. Among their duties, Plks control the assembly of centrosomes, tiny organelles that facilitate mitotic spindle assembly and maintain the fidelity of chromosome inheritance. Plks are overexpressed in cancer, and therefore it is critical to unravel the normal regulation of these kinases. Here, we studied Plk4 regulation whose activity controls centrosome number. We showed that, as do other Plks, Plk4 autoinhibits its kinase activity. However, Plk4 is unique in its ability to relieve autoinhibition through a third Polo box domain not present in other Plk family members. Moreover, autoinhibition controls Plk4 oligomerization, which ultimately governs its stability and thus centrosome duplication.