Polo-like kinase 1 (PLK1) phosphorylates a plethora of different substrates to regulate key cell cycle processes that include, among others, mitotic entry, chromosome condensation, nuclear envelope breakdown, centrosome maturation, spindle assembly and chromosome biorientation, cytokinesis, and the deposition of the specialized centromere histone CENP-A. Addressing the exact spatial and temporal control of PLK1 activity in these processes and its dynamic interplay with protein phosphatases that counteract mitotic phosphorylation, most notably PP1 and PP2A, has proven especially puzzling. In this review, we focus on the main unknowns in the area of human PLK1 regulation, exploring more specifically an emerging concept that master docking sites, including newly discovered noncanonical motifs, trigger initial local activation of PLK1 that promotes subsequent localized spreading of phosphorylation.

Nature Structural & Molecular Biology, Published online: 14 July 2025; doi:10.1038/s41594-025-01619-0BiP–glucose-regulated protein 94 chaperones are critical to the proper folding of secretory and transmembrane proteins. Brenner et al. provide biochemical and structural insight into a conserved mechanism of chaperone cooperation underlying this quality control process.