Regulatory phosphorylation sites in PLK4. The degron motif of PLK4 (highlighted in blue) is conserved with phosphorylation of its serine and threonine residues creating a binding site for the F-box protein β-TrCP, which forms part of the SCFβ-TrCP ubiquitin ligase complex. Upon SCFβ-TrCP binding, PLK4 is subsequently ubiquitinated and targeted to the proteasome for degradation. The identity of the kinase responsible for phosphorylating the two residues in the degron motif is currently unknown. Autophosphorylation plays a role in controlling the stability of PLK4 and it has been shown that the region spanning residues 282 to 305 of M. musculus PLK4 is heavily autophosphorylated. The precise identities of the residues autophosphorylated are not known and only potential sites can be proposed (marked in red). One of these sites, S305, is conserved and is autophosphorylated in H. sapiens PLK4 (marked in green), although it has no direct role in regulating the turn-over of the kinase directly because its mutation to an alanine does not increase the stability of the kinase. However, it does seem to play a role in centriole duplication with its mutation to a glutamate increasing the incidence of centriole amplification in PLK4-overexpressing cells.