Fig. 8: Model of the conformational regulation of PLK1.
From: Structural regulation of PLK1 activity: implications for cell cycle function and drug discovery
PLK1 is in an inactive state (red KD) when autoinhibited by a KD–PBD interaction or in a dimer promoted by PBD interactions. Binding of Bora relieves either form, but still retains PLK1 in an inactive state until recruitment of Aur-A which activates PLK1 through T210 phosphorylation (green KD). Phosphosubstrate binding has also been shown to lead to an increase in activity of PLK1. Monomeric PLK1 will be susceptible to degradation through exposure of the destruction box and Lys492 in the PBD (Fig. 1), Abbapolin PBD inhibitors have been shown to induce monomeric PLK1 and lead to their proteasomal degradation (left) [95]. ATP binding site inhibitors such as BI2536 induce a catalytically inactive open conformation of PLK1 [88, 89] (right).
