Maureen A. Powers, PhD
Department of Cell Biology
Office: 445 Whitehead Reseach Bldg
Phone: 404 727-8859
Emory University - Department of Cell Biology
615 Michael St, 1941/001/1AF
Atlanta, GA 30322
Research FocusThe research interests of my laboratory center on the function of the Nuclear Pore Complex (NPC) and its component proteins, the nucleoporins (Nups). The NPC is responsible for movement of proteins and RNAs between nucleus and the cytoplasm, a fundamental activity of the eukaryotic cell. This process is mediated by the NPC along with an extensive series of cargo receptors, the alpha and beta karyopherin families. Our long term goal is to understand how NPC function is regulated and tightly integrated with other cellular processes including nuclear organization, cell division and transcription.
We have largely, but not exclusively, focused on the unique nucleoporin, Nup98, which plays key roles both on and off the NPC. We showed that Nup98 moves dynamically between the NPC and the nucleoplasm and its mobility is linked to ongoing transcription. At the NPC, Nup98 is located at the center of the structure and plays roles in trafficking and, we propose, in the exclusion of non-nuclear proteins from the nucleus – the permeability barrier of the pore. More recently, Nup98 was shown to regulate transcription of a subset of genes in Drosophila. We are particularly interested in the mechanism of such regulation in vertebrate cells and the interaction of Nup98 with chromatin. We expect to extend this in the future to the interaction between other nucleoporins and chromatin.
The NPC is remarkably integrated with other key nuclear functions, in particular with mitosis. We have shown that Nup98 regulates microtubule dynamics within the mitotic spindle through an affect on the microtubule depolymerizing kinesin, MCAK. We have also shown that this influence is regulated in part by mitotic phosphorylation of Nup98.
An additional interest is the mechanism by which chromosomal translocations involving Nup98 lead to Acute Myelogenous Leukemia. In these translocations, the N-terminal nucleoporin repeat domain of Nup98 is fused to the C-terminus of one of a variety of nuclear proteins. This fusion partner is most often a member of the homeobox transcription factor family. The fusion proteins lead to aberrant transcriptional activation of genes, particularly HoxA9 and Meis, and this in turn contributes to leukemogenesis. We have shown that the leukemogeneic proteins have a novel localization within the nucleus during interphase and are targeted to kinetochores during mitosis. Additionally, the leukemogenic fusions can interact with and relocalize the endogenous Nup98. These activities may be additional factors in the ability of the fusion proteins to induce cancer.
Our work employs a variety of complementary approaches: biochemical assays, in vitro reconstitution of mitotic and interphase nuclear function using Xenopus egg extract, and sophisticated imaging analyses in both fixed and living cells. Through the combination of these approaches, we have made important contributions to novel facets of NPC function including nucleoporin dynamics, links to transcription, and regulation of mitosis. As increasing connections between nucleoporin mutations and disease, including leukemias, cardiac disease, and neurodegenerative diseases, continue to emerge, it is essential to understand how alterations in nucleoporins can impact nuclear transport and other functions to which nucleoporins make important contributions.