Regulation of the Minichromosome Maintenance Protein 3 (MCM3) Chromatin Binding by the Prolyl Isomerase Pin1. Issue 24 (7th December 2018)

• Record Type: Journal Article
• Authors: Schumann, Michael; Malešević, Miroslav; Hinze, Erik; Mathea, Sebastian; Meleshin, Marat; Schutkowski, Mike; Haehnel, Wolfgang; Schiene-Fischer, Cordelia
• Is Part Of: Journal of molecular biology. Volume 430:Issue 24(2018)
• Page Start: 5169
• Page End: 5181
• Publication Date: 2018-12-07
• Subjects: MCM minichromosome maintenance -- PPIase peptidyl prolyl cis/trans isomerase -- RB retinoblastoma protein -- ITC isothermal titration calorimetry; Pin1 -- MCM3 -- prolyl isomerase -- phosphorylation -- cell cycle; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.10.002
• Languages: English
• ISSNs: 0022-2836

Abstract

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.