Polo-Like Kinases: A Team in Control of the Division

Abstract

Polo, the founding member of the family of polo-like kinases (Plks) was identified in a Drosophila screen for mutants affecting spindle pole behavior.(1) Several mutants showed defects at their spindle poles and were hence named after the magnetic poles of the earth or geo-magnetic phenomena associated with them, like Polo and Aurora. Currently, the conserved family of Plks consists of many members throughout various species. Multiple Plks are present in mammalian cells (Plk1, Plk2/Snk, Plk3/Fnk/Prk, and Plk4/Sak) and Xenopus (Plx1-3), whereas in other species only one member has been identified, like Polo in Drosophila, Cdc5 in budding yeast and Plo1 in fission yeast. Plks are now viewed as important regulators of multiple functions before and during the mitotic cell division. In this review, we will focus our attention on human Plk1 and its family members Plk2-4 and the many roles they play during mitosis. Furthermore, we will describe the currently knowledge of the regulation of these functions.

Combinatorial inhibition of Plk1 and PKCβ in cancer cells with different p53 status

“…Plk1 has predictive and prognostic value for patients with diverse cancers [22,23]. The importance of Plk1 as a measure for the aggressiveness of a tumor results from its important role for the mitotic checkpoints of cancer cells [24-28]. Interfering with Plk1 activity and/or expression with dominant-negative mutants, antibody microinjection, antisense oligonucleotides or small interfering RNAs leads to different mistakes in centrosomal maturation, mitotic catastrophe, increased apoptosis and tumor inhibition in cancer cells [23,27,29-38].…”

Mutations in Drosophila Greatwall/Scant Reveal Its Roles in Mitosis and Meiosis and Interdependence with Polo Kinase

“…It also functions at the kinetochore-microtubule interface to monitor tension; the 3F3/2 phospho-epitope seen on kinetochores in the absence of tension is a consequence of Plk1/Plx1 kinase activity in vertebrates [6,7]. Removal of cohesins from chromosomal arms in mitosis and meiosis also requires phosphorylation of cohesin subunits by Polo kinases (reviewed by [8]). In Drosophila meiosis II, Polo phosphorylates and inactivates the centromeric cohesion protector protein Mei-S332 [9].…”

Bioorthogonal Probes for Polo‐like Kinase 1 Imaging and Quantification

“…Specific functions of PLK1 during mitosis include chromosome segregation, centrosome maturation, bipolar spindle formation, regulation of the anaphase-promoting complex/cyclosome (APC/C), coordination of cytokinesis, and regulation of the DNA damage checkpoint. [1][2][3] This serine/threonine kinase also plays an essential role in mitotic entry by promoting Cdk1-cyclin B activation and nuclear translocation through phosphorylation of Cdc25C, [4,5] Wee1, [6] Myt1, [7] and cyclin B. [8,9] PLK1 consists of two domains, an N-terminal catalytic serine/threonine kinase domain and a C-terminal polo-box domain (PBD).…”

“…[8,9] PLK1 consists of two domains, an N-terminal catalytic serine/threonine kinase domain and a C-terminal polo-box domain (PBD). [3] The PBD recognizes specific phosphorylated targeting sequences that are essential for interaction of PLK1 with its substrates and for PLK1 localization to centrosomes, spindles, kinetochores, and the midzone/midbody during mitosis. [10][11][12][13] Given the role of PLK1 in mitotic progression it is perhaps not surprising that overexpression has been shown to lead to oncogenic transformation.…”