1983 B.A. Boston University, Biology

1992 Ph.D. Duke University, Cell Biology and Genetics

• cell cycle regulation
• mitotic exit
• cytokinesis
• daughter cell-specific gene expression
• polarized growth

Cell division is a fundamental and highly regulated process that is essential for the propagation of all living organisms. Errors in cell division can cause cellular death, lead to developmental defects or create favorable conditions for cancer development. Indeed, two major hallmarks of cancer are increased genomic instability and unrestrained cell division, which are brought about by errors in cell cycle regulation. Therefore, research on cell cycle regulation is critical for resolving the molecular mechanisms of cancer. My lab employs multidisciplinary approaches, including yeast genetics and molecular biology, to study conserved elements of cell cycle regulation. Our research using the budding yeast Saccharomyces cerevisiae implicates the Mob protein family in regulating critical aspects of cell division and cell development. S. cerevisiae Mob1 is a component of a conserved regulatory network termed the Mitotic Exit Network (MEN) that functions to coordinate diverse events associated with mitotic exit, such as cyclin dependent kinase inactivation, cytokinesis and G1 gene transcription. Mob1 localizes to yeast centrosomes and the cytokinesis ring during late mitosis and interacts with two important regulatory proteins, the MEN protein kinase Dbf2 and Mps1, a protein kinase required for mitotic checkpoint regulation and centrosome duplication. Mutations in Mob1 cause mitotic arrest, cytokinesis and genomic instability defects. Similar genomic instability in mammalian cells would greatly increase the risk for cancer development.

We recently discovered that a second S. cerevisiae Mob protein, Mob2, is a component of a novel and conserved signaling network, termed RAM for Regulation of Ace2-dependent transcription and Morphogenesis. The RAM network regulates 1) polarized growth by maintaining the polarity of the actin cytoskeleton and 2) the localization and activity of Ace2 transcription factor, which regulates a subset of genes in only one of the two cell division products. Mob2 binds the Dbf2-related protein kinase Cbk1 and both proteins localize to sites of cortical growth and to the daughter cell nucleus. Our data suggests that the Mob2-Cbk1 complex acts late in RAM signaling and may directly regulate the daughter cell-specific localization and function of Ace2 transcription factor. We are currently expanding our research to investigate MEN and RAM-like signaling networks in mammalian cells, with the expectation that those networks are critical for mammalian cell division and development.

Stavridi, E.S., Harris, K.G., Huyen, Y., Verwoerd, P., Stayrook, S.E., Jeffrey, P.D., Pavletich, N.P. and Luca, F.C. (2003) Crystal structure of human Mob1 protein; toward understanding Mob-regulated cell cycle pathways. Structure IN PRESS

Weiss, E.L., Kurischko, C., Zhang, C., Shokat, K., Drubin, D.G. and Luca, F.C. (2002) The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell-specific localization of Ace2p transcription factor. J. Cell Biol. 158: 885 - 900

Luca, F.C., Mody, M., Kurischko, C., Roof, D.M., Giddings, T.H. and Winey, M. (2001). Saccharomyces cerevisiae Mob1p is required for cytokinesis and mitotic exit. Mol. Cell. Biol. 20: 6972 – 6983

Komarnitsky, S.I., Chiang, Y-C., Luca, F.C., Chen, J., Toyn, J.H., Winey, M., Johnston, L.H., and Denis, C. (1998) DBF2 protein kinase binds to and acts through the cell cycle-regulated MOB1 protein. Mol. Cell. Biol. 18: 2100 - 2107

Luca, F.C. and Winey, M. (1998). MOB1, (Mps One Binder-1), an essential yeast gene required for the completion of mitosis and maintenance of ploidy. Mol. Biol. Cell. 9: 29 - 46