Polo-like kinase 4: the odd one out of the family

Abstract Polo-like kinase 4 (PLK4) is a unique member of the Polo-like family of kinases that shares little homology with its siblings and has an essential role in centriole duplication. The turn-over of this kinase must be strictly controlled to prevent centriole amplification. This is achieved, in part, by an autoregulatory mechanism, whereby PLK4 autophosphorylates residues in a PEST sequence located carboxy-terminal to its catalytic domain. Phosphorylated PLK4 is subsequently recognized by the SCF complex, ubiquitinylated and targeted to the proteasome for degradation. Recent data have also shown that active PLK4 is restricted to the centrosome, a mechanism that could serve to prevent aberrant centriole assembly elsewhere in the cell. While significant advances have been made in understanding how PLK4 is regulated it is certain that additional regulatory mechanisms exist to safeguard the fidelity of centriole duplication. Here, we overview past and present data discussing the regulation and functions of PLK4.