Timely and error-free progression of the cell cycle is fundamental to the development and proper function of eukaryotic organisms. As such, eukaryotes have evolved complex regulatory mechanisms to facilitate development and cell maintenance. Our studies are focused on an evolutionarily conserved family of mitotic proteins called the Aurora kinases. These proteins comprise a class of serine/threonine kinases that are essential for mitotic events such as centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis (Andrews et. al., 2003). AIR-2, the C. elegans homolog of Aurora B, has been shown to interact with a variety of substrates to facilitate processes such as chromosome segregation and cytokinesis. Depletion of AIR-2 via RNA-mediated interference (RNAi) leads to embryonic lethality at the one cell stage (Schumacher et. al., 1998). A temperature-sensitive (ts) mutation, air-2 (or207ts) confers a similar phenotype at restrictive temperatures (Severson et. al., 2000). Our current goal is to elucidate the AIR-2 regulatory pathway by identifying the components working in concert with AIR-2. We therefore conducted a genome-wide RNAi screen to identify suppressors of air-2(or207ts) lethality. We have screened through an RNAi construct library comprising nearly every gene in the C. elegans genome (approximately 17,000 genes). The strongest RNAi suppressor identified from this screen encodes a putative C. elegans AAA-ATPase and confers ~72.6% viability to the air-2(or207ts) strain at 20ºC as compared with 1% viability for air-2(or207ts) alone. For simplicity purposes, we have tentatively named this suppressor abs-1 (Aurora B Suppressor-1). To understand the relationship between air-2 and abs-1, functional analyses are being performed. In vitro binding and kinase assays reveal that ABS-1 can bind directly to AIR-2 and inhibit its kinase activity. In addition, Western analysis revealed that AIR-2 levels are stabilized in abs-1(RNAi) embryo extracts as compared to controls. Furthermore, immunostaining studies reveal that AIR-2 localization is disrupted in abs-1(RNAi) embryos. Hence, our data suggests that abs-1(RNAi) can suppress the air-2(or207ts) lethality by stabilizing AIR-2 levels and by controlling the localization and kinase activity of AIR-2. We are therefore examining the possibility that the AIR-2 complex is regulated by ABS-1 via proteolytic and non-proteolytic pathways.