|
| |
Biographical Sketch
Dr. Rundell received her
undergraduate degree in biology at the University of Rochester, then completed
her PhD degree in 1973 at Case Western Reserve University, where she studied
microbial physiology. She began to study animal viruses as a postdoctoral fellow
with Dr. Peter Tegtmeyer, first at Case Western Reserve and then at SUNY, Stony
Brook. There she was involved in studies that defined the tumor antigens of
SV40, an interest she continued to pursue and expanded on when she joined the
faculty of Northwestern University in 1976.
|
|
Research Description
Structure and function of the small-t
antigen of simian virus 40; regulation of cell growth by the SV40 small-t and large-T
antigens, with particular emphasis on their effects on cell cyclins, cyclin-dependent
kinases, and the cyclin kinase inhibitors, as well as the cellular phosphatase PP2A.
|
Research Abstract
 This laboratory studies the small-t antigen of simian virus 40, a viral protein that enhances the growth of cells leading to efficient viral replication and oncogenic
transformation. Small-t antigen functions in part through its interaction with two cellular proteins, now known to be subunits of cellular phosphatase 2A (PP2A). We have shown that small-t binds and inhibits PP2A, leading to increased phosphorylation of many target proteins including MAPK and
MEK. A second, genetically separable, activity of small-t antigen is the transcriptional activation of the cyclin A promoter. The resulting increase in cyclin A is one of the factors that leads to growth promotion by small-t.
This may be related to another activity of small-t, the decrease in levels of the cyclin kinase inhibitor p27 in cells.
Small-t and large-T antigens work in concert to drive cell growth of contact-inhibited cells and to allow growth of some
normally adherent cells under anchorage-free conditions. Small-t has been found to be essential for transformation in several human cell systems. Currently, this laboratory focuses on virus interactions with primary mesothelial, based on reports that SV40 may be present in a large fraction of
mesothelioma tumors. We have found that large-T and telomerase can immortalized these cells but that transformation requires small-t. Small-t also have a major role in maintaining episomal viral genomes in
these cells and cells without small-t have little more than one copy per cell. Cells with small-t contain 100-1000 copies of the episomal genome. Mechanisms that promote this are under investigation.
|
Publications
Skoczylas, C., B. Henglein and K. Rundell. 2005. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is
mediated by a cell-cycle regulated E2F site. Virology 332: 596-601.
Shaikh, S., C. Skoczylas, R. Longnecker and K. Rundell. 2004. Inability of simian virus 40 to establish productive
infection of lymphoblastic cell lines. J. Virol. 78: 4917-4920.
Skoczylas, C., K.M. Fahrbach and K. Rundell. 2004. Cellular targets of the SV40 small-t antigen in human cell
transformation. Cell Cycle 3: e44-e48.
Boyapati, A., M. Wilson, J. Yu
and K. Rundell. 2003. SV40 17KT antigen complements dnaJ mutations in large T antigen to restore transformation of primary human fibroblasts. Virology 315: 148-158. |
|
