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 Faculty Mentors |
Research efforts of the Cerione laboratory have focused on understanding molecular mechanisms by which signals are transmitted from cell surface receptors to biological effectors. In particular, Dr. Cerione and his colleagues have been interested in identifying new signaling molecules that influence the growth and differentiation of mammalian cells. Three areas of research are currently being pursued. The first involves studies of the regulation and structural characterization of a cell-division-cycle, Ras-related GTP-binding protein, Cdc42. This protein and its regulators appear to have critical roles in cell growth, the establishment of cell polarity, and cytokinesis. The Cerione group is using biochemical, molecular-biology-based, and structural techniques to obtain new insights into how this Ras-like protein, through interactions with a variety of cellular targets, can coordinate cytoskeletal changes with cell cycle progression and cell division. A second area of research focuses on structure-function comparisons of heterotrimeric G proteins and Ras-like GTP-binding proteins. Here the retinal G protein, transducin, is used as a model for developing novel fluorescence approaches to study G protein activation and G protein-target interactions. The third area of interest concerns the identification and structure-function characterization of novel GTP-binding activities present in the nucleus and engaged in regulating RNA metabolism and/or cell cycle progression. Two such nuclear activities are being studied. One is an 80 kDa dual function GTP-binding protein/transglutaminase which appears to be regulated by retinoic acid under conditions of cellular apoptosis. The second is an 18 kDa RNA cap-binding protein, CBP20, which has an essential role in the splicing of precursor messenger RNA and in certain aspects of RNA nucleocytoplasmic transport. The Cerione group has shown that certain growth factor receptor tyrosine kinases can initiate signaling pathways that lead to the nucleus and culminate in stimulation of the GTP-binding and RNA cap-binding activity of CBP20. They are now attempting to delineate the molecular mechanisms underlying the regulation of each of these nuclear GTP-binding activities. In pursuing each of these areas of research, use is made of a combination of biophysical and molecular biology-based approaches to obtain a comprehensive representation of how growth factor receptors and GTP-binding proteins mediate communication between the plasma membrane and the nucleus. In many cases, this has involved developing fluorescence spectroscopic approaches (e.g. resonance energy transfer, fluorescence anisotropy) to directly monitor protein-protein interactions that comprise different signaling pathways. More recently, X-ray crystallographic analysis has been used to obtain detailed information regarding the protein interfaces involved in signaling interactions. The ultimate goal is to utilize this information to design new classes of dominant-negative mutant signaling molecules that will serve as powerful reagents for in vivo studies. Recent Publications:
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