Regulation of the Minichromosome Maintenance Protein 3 (MCM3) Chromatin Binding by the Prolyl Isomerase Pin1. Issue 24 (7th December 2018) - Schumann, Michael
Abstract: Human Pin1 is a peptidyl prolyl cis / trans isomerase with a unique preference for phosphorylated Ser/Thr-Pro substrate motifs. Here we report that MCM3 (minichromosome maintenance complex component 3) is a novel target of Pin1. MCM3 interacts directly with the WW domain of Pin1. Proline-directed phosphorylation of MCM3 at S112 and T722 are crucial for the interaction with Pin1. MCM3 as a subunit of the minichromosome maintenance heterocomplex MCM2–7 is part of the pre-replication complex responsible for replication licensing and is implicated in the formation of the replicative helicase during progression of replication. Our data suggest that Pin1 coordinates phosphorylation-dependently MCM3 loading onto chromatin and its unloading from chromatin, thereby mediating S phase control. Graphical Abstract: Highlights: The prolyl isomerase Pin1 physically interacts with the pre-replication complex component MCM2–7 via MCM3. The WW domain of Pin1 interacts with MCM3 in a phosphorylation-dependent manner. Pin1 catalyzes the prolyl cis / trans isomerization in MCM3-derived peptides. Pin1 regulates chromatin localization of MCM3 in a cell cycle-dependent manner.