Journal Article

Polo-like kinases: structural variations lead to multiple functions

Guerrero, Adán, Zitouni, Sihem, Jana, Swadhin Chandra, Bettencourt-Dias, Mónica, Nabais, Catarina

2014

Overview

Key Points Polo-like kinases (PLKs) are a family of Ser/Thr kinases that have a pivotal role in cell cycle progression, the centrosome cycle, mitosis and cellular responses to DNA damage, which makes them attractive targets for treatments against several diseases. PLK1 is the most ancestral and best-conserved member of the family; it is found in most eukaryotic organisms, except for higher land plants. PLK4 is the most divergent member of the family. PLK2, PLK3 and PLK5 have evolved very recently, probably from a PLK1 gene duplication in vertebrates. PLK1 and PLK4 have distinct structural organizations and are phosphorylated at different residues, which correlate with different mode of actions. The amino-terminal kinase domain and carboxy-terminal polo box domains that characterize PLKs are crucial for regulation of their kinase catalytic activity in time and space, and for controlling subcellular PLK localization. Recent studies show non-canonical functions for PLKs in asymmetric cell division and cilia disassembly. PLKs function in centriole and centrosome biogenesis; PLK1 integrates various external stimuli with cell cycle inputs to coordinate mitotic progression and the centrosome cycle, whereas PLK4 drives centriole assembly. PLK2 and PLK3 have roles in DNA replication and in the DNA damage response and are also expressed in non-proliferative tissues, in which they have a role in cell differentiation and homeostasis (for example, PLK2 and PLK5 regulate neuronal activity). Members of the polo-like kinase (PLK) family are crucial regulators of cell cycle progression, centriole duplication, mitosis, cytokinesis and the DNA damage response. Recent structural and molecular studies have revealed how such processes depend on the tight regulation of PLK abundance, activity, localization and interactions with other proteins, and how dysregulation may be associated with disease. Members of the polo-like kinase (PLK) family are crucial regulators of cell cycle progression, centriole duplication, mitosis, cytokinesis and the DNA damage response. PLKs undergo major changes in abundance, activity, localization and structure at different stages of the cell cycle. They interact with other proteins in a tightly controlled spatiotemporal manner as part of a network that coordinates key cell cycle events. Their essential roles are highlighted by the fact that alterations in PLK function are associated with cancers and other diseases. Recent knowledge gained from PLK crystal structures, evolution and interacting molecules offers important insights into the mechanisms that underlie their regulation and activity, and suggests novel functions unrelated to cell cycle control for this family of kinases.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/641/2090 / 631/80/128/1965 / 631/80/641 / 631/80/641/1655 / Animals / Biochemistry / Biosynthesis / Cancer Research / Cell Biology / Cell cycle / Cell Cycle Proteins - chemistry / Cell Cycle Proteins - metabolism / Cell division / Cellular control mechanisms / Crystals / Cyclin-dependent kinases / Deoxyribonucleic acid / Developmental Biology / DNA / Gene Expression Regulation / Genetic aspects / Humans / Kinases / Life Sciences / Localization / Models, Molecular / Phosphotransferases / Phylogenetics / Polo-Like Kinase 1 / Properties / Protein Serine-Threonine Kinases - chemistry / Protein Serine-Threonine Kinases - metabolism / Protein Stability / Protein Structure, Secondary / Proteins / Proto-Oncogene Proteins - chemistry / Proto-Oncogene Proteins - metabolism / review-article / Stem Cells / Structure / Yeast