Cyclin-dependent kinase CDK1 targets cell-cell junction components and governs epithelial monolayer integrity throughout the cell cycle

Abstract

The cyclin-dependent kinase CDK1 is a master regulator of cell cycle progression and the associated changes in cell shape. The biochemical functions of CDK1 have been primarily studied in cultured cells lacking adhesion to their neighbors. Within epithelial layers, cells are tightly connected, and cell cycle-associated shape changes must occur without compromising epithelial barrier function. Here, we showed that a pool of CDK1 localized to cell-cell contacts in cultured epithelial cells and phosphorylated substrates at cell-cell junctions throughout the cell cycle. CDK1 substrates identified by proteomic analysis included various components of adherens junctions, tight junctions, and desmosomes, as well as proteins that link cell-cell adhesion complexes to the actomyosin cytoskeleton. CDK1 activity maintained the linear organization of cell-cell junctions and was essential for preserving the integrity of the epithelial barrier. These findings expand the role of CDK1 to the regulation of cell-cell adhesion, establishing that the machinery that governs the cell cycle also controls epithelial integrity.