Polo-like kinase 1 (PLK1), the prototypical member of the polo-like family of serine/threonine kinases, is a pivotal regulator of mitosis and cytokinesis in eukaryotes. Many layers of regulation have evolved to target PLK1 to different subcellular structures and to its various mitotic substrates in line with its numerous functions during mitosis. Collective work is starting to illuminate an important set of substrates for PLK1: the mitotic kinases that together ensure the fidelity of the cell division process. Amongst these, recent developments argue that PLK1 regulates the activity of the histone kinases Aurora B and Haspin to define centromere identity, of MPS1 to initiate spindle checkpoint signaling, and of BUB1 and its pseudokinase paralog BUBR1 to coordinate spindle checkpoint activation and inactivation. Here, we review the recent work describing the regulation of these kinases by PLK1. We highlight common themes throughout and argue that a major mitotic function of PLK1 is as a master regulator of these key kinases.

Objectives— Several findings argue for a protective effect of high-density lipoproteins (HDLs) against endothelial dysfunction. The molecular mechanisms underlying this protective effect are not fully understood, although recent works suggest that the actions of HDL on the endothelium are initiated by multiple interactions between HDLs (lipid or protein moiety) and cell surface receptors. We previously showed that the mitochondrial related F 1 -ATPase is a cell surface receptor for HDLs and their main atheroprotective apolipoprotein (apoA-I). Herein we test the hypothesis that the cell surface F 1 -ATPase may contribute to the ability of apoA-I and HDLs to maintain endothelial cell survival. Methods and Results— Cell imaging and binding assays confirmed the presence of the F 1 -ATPase at the surface of human umbilical vein endothelial cells (HUVECs) and its ability to bind apoA-I. Cell surface F 1 -ATPase activity (ATP hydrolysis into ADP) was stimulated by apoA-I and was inhibited by its specific inhibitor IF 1 -H49K. Furthermore the antiapoptotic and proliferative effects of apoA-I on HUVECs were totally blocked by the F 1 -ATPase ligands IF 1 -H49K, angiostatin and anti-βF 1 -ATPase antibody, independently of the scavenger receptor SR-BI and ABCA1. Conclusion— This study suggests an important contribution of cell surface F 1 -ATPase to apoA-I-mediated endothelial cell survival, which may contribute to the atheroprotective functions of apoA-I.