Abstract

This is an application for a Research Career Development Award designed to promote the development of Dr. Shannon Kenney's independent research career. Dr. Kenney's research interests have focused around the regulatory proteins of the Epstein-Barr virus (EBV). In previous work in her laboratory she has investigated the mechanisms whereby the EBV immediate-early (IE) proteins control EBV replication. In addition, an ongoing interest of her laboratory has been the ability of these EBV-encoded proteins to regulate important cellular and HIV genes. The particular project in this grant application investigates the mechanism(s) whereby the EBV BRLF1 IE protein activates c-myc expression. The possibility that BRLFl-induced activation of c-myc is important in the development of AMS-related lymphomas is suggested by A) the high frequency of EBV-positive lymphomas in AIDS patients, B) the expression of replicative EBV functions in these lymphomas, and C) the previously demonstrated ability-of activated c-myc to synergistically with EBV-encoded transforming functions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA001711-03
Application #
2084336
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1992-08-01
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Zhang, Q; Holley-Guthrie, E; Ge, J Q et al. (1997) The Epstein-Barr virus (EBV) DNA polymerase accessory protein, BMRF1, activates the essential downstream component of the EBV oriLyt. Virology 230:22-34
Hong, Y; Holley-Guthrie, E; Kenney, S (1997) The bZip dimerization domain of the Epstein-Barr virus BZLF1 (Z) protein mediates lymphoid-specific negative regulation. Virology 229:36-48
Zalani, S; Coppage, A; Holley-Guthrie, E et al. (1997) The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter. J Virol 71:3268-74
Rogers, R P; Ge, J Q; Holley-Guthrie, E et al. (1996) Killing Epstein-Barr virus-positive B lymphocytes by gene therapy: comparing the efficacy of cytosine deaminase and herpes simplex virus thymidine kinase. Hum Gene Ther 7:2235-45
Zalani, S; Holley-Guthrie, E; Kenney, S (1996) Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proc Natl Acad Sci U S A 93:9194-9
Zhang, Q; Hong, Y; Dorsky, D et al. (1996) Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication. J Virol 70:5131-42
Zalani, S; Holley-Guthrie, E; Kenney, S (1995) The Zif268 cellular transcription factor activates expression of the Epstein-Barr virus immediate-early BRLF1 promoter. J Virol 69:3816-23
Zhang, Q; Gutsch, D; Kenney, S (1994) Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency. Mol Cell Biol 14:1929-38
Gutsch, D E; Holley-Guthrie, E A; Zhang, Q et al. (1994) The bZIP transactivator of Epstein-Barr virus, BZLF1, functionally and physically interacts with the p65 subunit of NF-kappa B. Mol Cell Biol 14:1939-48
Gutsch, D E; Marcu, K B; Kenney, S C (1994) The Epstein-Barr virus BRLF1 gene product transactivates the murine and human c-myc promoters. Cell Mol Biol (Noisy-le-grand) 40:747-60