The goal of this application for the NCI Clinical Investigator Award is to provide a transition for Dr. Steussy from his successful clinical career as a family practitioner to that of a scientifically qualified clinical investigator. The proposed project is to uncover the structure/function relationships of the yeast ubiquitin conjugating enzyme Cdc34 and it recently cloned human equivalent. The specific hypothesis is that knowledge of the three dimensional structure and kinetic parameters of normal Cdc34 and some critical point mutations will illuminate the chemical mechanism and control of this vital cell cycle enzyme. The proposed study is significant because Cdc34 is an incompletely understood enzyme that performs an essential role in the normal cell cycle and as a downstream effector for the oncogene p53. A complete understanding of this enzyme is fundamental to understanding normal cell cycle control and the etiology of carcinogenesis. After five years in rural clinical practice Dr. Steussy has elected to begin a career in scientific research. His M.D. was granted by Indiana University in 1981, and he completed a residency in Family Practice at the University of Minnesota in 1984. After five years of engaging clinical practice in an underserved area of rural Tennessee he began graduate study here at Indiana University. In the last two and a half years he has made substantial progress on cloning and purifying Cdc34, cloning and purifying its upstream activator E1, and developing an activity assay. In order to bring his scientific fund of knowledge up to date he completed the core classroom requirements of the Department of Biochemistry for the Ph.D. degree and passed the departmental qualifying exam. Much of the strength of this project comes from its particular sponsors and the Department of Biochemistry. The sponsors, Dr. Goebl and Dr. Hamilton, are both experienced and well respected in their fields. Outstanding educators as well as extensively published researchers they make a superb team to guide Dr. Steussy through this project and see to his training as a competent independent investigator
| Liu, Y; Mathias, N; Steussy, C N et al. (1995) Intragenic suppression among CDC34 (UBC3) mutations defines a class of ubiquitin-conjugating catalytic domains. Mol Cell Biol 15:5635-44 |
| Zhou, K; Takegawa, K; Emr, S D et al. (1995) A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum: biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs during growth and development. Mol Cell Biol 15:5645-56 |
