The regulation of keratin 8 by aurora B during the cell cycle

Cell division is required for living organisms to carry out their most basic functions, such as transmitting genetic information to the future generation. The morphology and biochemistry of a cell changes dramatically during cell division. Dynamic changes occur in multiple components of the cell including chromosomes, membranous organelles and cytoskeletal elements during mitosis and cytokinesis. Various cell cycle-dependent kinases strictly regulate these intricate activities. The molecular details of regulatory mechanisms during cell division and master regulators and their dynamic targets are active research questions in cell division. Microtubule and actin filaments are two main elements of the cytoskeleton that play critical roles in mitosis and cytokinesis and have relatively well-understood in terms of their functions and regulatory mechanisms. In contrast, intermediate filaments, a type of cytoskeletal element, are a less well-studied component of cell division. Keratins are the most diverse family of intermediate filaments. They are expressed in tissue-specific manner. Additionally, they are used as a biomarker in cancer diagnosis because of their differential expression in malignant tissues. The primary function of keratins is to provide mechanical strength to the cell. However, how the Keratins are re-organized during cell division and their regulatory mechanisms are not well studied. I aimed to investigate how the master mitotic kinases regulate keratins during mitosis and cytokinesis by using both proteomic and cell biology-based approaches. Our mass spectrometry analysis revealed six Aurora B kinase-dependent phosphorylation sites of Keratin 8. By creating phospho-mutant versions, I analyzed and characterized the roles of the phosphorylation site of Keratin 8 during mitosis and cytokinesis. Our study provides insight into the function and regulation of Keratin 8 during cell division. We showed that cytokinesis-specific phosphorylation of Keratin 8 is required for successful cytokinesis by reorganizing Keratin 8 fibers by Aurora B kinase.