From Plk1 to Plk5 Functional evolution of Polo-like kinases

Mammalian Polo-like kinases (Plks) are characterized by the presence of an N-terminal protein kinase domain and a C-terminal Polo Box Domain (PBD) involved in substrate binding and regulation of kinase activity. Plk1-4 have traditionally been linked to cell cycle progression, genotoxic stress and, more recently, neuron biology. Recently, a fifth mammalian Plk family member, Plk5, has been characterized in murine and human cells. Plk5 is expressed mainly in differentiated tissues such as the cerebellum. Despite apparent loss of catalytic activity and a stop codon in the middle of the human gene, Plk5 proteins retain important functions in neuron biology. Notably, its expression is silenced by epigenetic alterations in brain tumors such as glioblastomas, and its re-expression prevents cell proliferation of these tumor cells. In this review, we will focus on the non-cell cycle roles of Plks, the biology of the new member of the family, and the possible kinase-and PBD-independent functions of Polo-like kinases.