Eileen White
	Professor Department of Molecular Biology and Biochemistry Rutgers, The State University of New Jersey Associate Director for Basic Science Cancer Institute of New Jersey Adjunct Professor Department of Surgery, UMDNJ-RWJMS Ph.D., 1983, SUNY, Stony Book, NY Tel:  [732] 235-5329 Fax: [732] 235-5795 ewhite@cabm.rutgers.edu http://white.cabm.rutgers.edu/

Adenovirus, p53, apoptosis, oncogenes, programmed cell death, tumor suppressor genes, cancer, E1B, Bcl-2, cell cycle, caspase.

Regulation of Apoptosis by Viral Oncogenes

Primary epithelial cells become transformed as a result of the combined action of deregulation of cell cycle control and inhibition of programmed cell death (apoptosis). Expression of the human adenovirus (Ad2/5) E1A oncogene releases normal restrictions on cell cycle progression through interactions with the retinoblastoma tumor suppressor protein and its relatives, and with the p300 and CBP transcriptional co-activators. The cellular response to this deregulation of cell growth control by E1A is the stabilization of the p53 tumor suppressor protein and the induction of p53-dependent apoptosis. The activation of this apoptotic program prevents transformation and can diminish virus replication. The adenonvirus E1B oncogene encodes two proteins (E1B 19K and 55K) that function to inhibit apoptosis, which thereby sustains transformation and productive infection. E1B 55K functions by interacting with and inhibiting p53, whereas E1B 19K is a viral Bcl-2 homologue which functions as a general apoptosis inhibitor by binding to and inhibiting components of the apoptotic machinery. The long-term focus of the White laboratory has been to determine the mechanism by which E1A induces, and E1B 19K inhibits, apoptosis. As deregulation of apoptosis is a common feature of many disease states, knowledge gained by this pursuit should provide new opportunities for the development of novel therapies, particularly for cancer treatment. More information can be obtained from the White Laboratory Website.

Selected Publications1