The aneuploidy that is phenotypic of many cancer cells can result from defects in chromosome segregation or failures in cytokinesis. The investigator is using C. elegans as a model system to study the role of chromosomes and the mitotic spindle midzone in the stabilization of the cleavage furrow and the completion of cytokinesis. The C. elegans AIR-2 kinase appears to have an important role in these events. AIR-2 is initially localized to metaphase chromosomes, but moves to the spindle midzone at anaphase. Disruption of AIR-2 expression results in the production of unicellular embryos that execute multiple cell cycles in the absence of cytokinesis. The investigator hypothesizes the AIR-2 kinase is an upstream component of the signaling pathway between the midzone microtubules and the cell cortex that is required for the completion of cytokinesis. The movement of AIR-2 from the chromosomes to the spindle midzone may recruit other proteins to the midzone that are downstream components of this signaling cascade. The current experimental goals are to identify these proteins as well as those acting upstream oI AIR-2 that arc required for the dynamic subcellular localization of AIR-2. The molecular components of the AIR-2 pathway will be identified by: 1) examining the relationship between the AIR-2 kinase and Eg5, a motor protein that is localized to the spindle midzone, 2) cloning the genes for five mutants that phenocopy loss of AIR-2 expression, 3) performing molecular screens for substrates and other proteins that interact with the AIR-2 kinase, 4) isolating extragenic enhancers and suppressors of a temperature-sensitive hypomorphic allele of air-2. The delineation of the AIR-2 regulatory pathway in C. elegans may lead to an understanding of, and the ability to interfere with, the oncogenic potential of the mammalian orthologs of AER-2.
Showing the most recent 10 out of 13 publications
