Dissecting the Mechanisms of Cell Division

Abstract

Human cell division is a highly coordinated set of events that ensures the proper transmission of genetic material from one mother cell to two newly formed daughter cells. Key to this process is the proper assembly and functioning of the mitotic microtubule spindle, which relies on a multitude of protein complexes, protein‐protein interactions, and regulatory mechanisms driven by enzymatic activities. Cell division is an essential step in cellular proliferation and misregulation of the cell division machinery can lead to premature sister chromatid separation, chromosomal instability, aneuploidy (a hallmark of many types of cancers) and resistance to cancer therapeutics like antimitotics. Therefore, understanding what the full complement of the cell division machinery is, what their functions are, how they are regulated, and how they cooperate to ensure proper cell division is critical to understanding cell division, tumorigenesis and the response of tumor cells to antimitotic drugs. Here, we present our integrative computational, chemical, proteomic, and genetic approaches to dissect the mechanisms governing cell division and for developing novel cancer therapeutics. We highlight our proteomic approaches to identify novel mitotic microtubule associated proteins with critical roles in cell division and for generating affinity and proximity protein association networks to interrogate their functions. We discuss our efforts to chemically dissect the cell cycle with an emphasis on the discovery of novel cell division inhbitors that can be used to dissect the mechanisms of cell division and for developing new cancer drugs. We are optimistic that our studies will increase our understanding of the mechanisms that ensure proper cell division and how their misregulation can lead to tumorigenesis and chemotherapeutic resistance.Support or Funding InformationThis work was funded by NSF MCB1243645, NIH R01GM117475‐01, ACS 123880‐RSG‐13‐398‐01‐CCG, a Cottrell Scholar Award from the Research Corporation for Science Advancement (RCSA), a V Scholar Award from the V Foundation for Cancer Research and a Basil O'Connor Award from the March of Dimes Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.