Abstract

The E1A and E1B oncogenes of adenovirus function during infection and transformation to control cell proliferation and apoptosis. E1A stimulates cell cycle progression by binding to Rb family members and to p300, which induces accumulation of p53 and leads to apoptosis. The E1B 19K protein, a member of the Bcl-2 family of apoptosis regulators, inhibits apoptosis and sustains virus infection. Induction of apoptosis by p53 is a complex process, involving many potential players, including Bax (an inducer of apoptosis) and the ICE family of cysteine proteases. The applicant will define the mechanism by which E1A induces the accumulation of p53, will identify the functional requirements within p53 for activation of cell death, and will determine the relationship between p53 function and activation of the ICE family proteases. The long term goal of the work is to study this important mechanism of tumor suppression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA060088-06
Application #
2871800
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Wong, May
Project Start
1994-03-01
Project End
2002-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Type
Schools of Medicine
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901

  Publications

Kimmelman, Alec C; White, Eileen (2017) Autophagy and Tumor Metabolism. Cell Metab 25:1037-1043
Guo, Jessie Yanxiang; White, Eileen (2013) Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors. Autophagy 9:1636-8
Henry, Holly; Thomas, Anju; Shen, Yan et al. (2002) Regulation of the mitochondrial checkpoint in p53-mediated apoptosis confers resistance to cell death. Oncogene 21:748-60
Sullivan, Gregory F; Garcia-Welch, Adrienne; White, Eileen et al. (2002) Augmentation of apoptosis by the combination of bleomycin with trifluoperazine in the presence of mutant p53. J Exp Ther Oncol 2:19-26
Degenhardt, Kurt; Chen, Guanghua; Lindsten, Tullia et al. (2002) BAX and BAK mediate p53-independent suppression of tumorigenesis. Cancer Cell 2:193-203
Cuconati, Andrea; White, Eileen (2002) Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes Dev 16:2465-78
Thomas, A; Giesler, T; White, E (2000) p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway. Oncogene 19:5259-69
Chiou, S K; White, E (1998) Inhibition of ICE-like proteases inhibits apoptosis and increases virus production during adenovirus infection. Virology 244:108-18
Thomas, A; White, E (1998) Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53 apoptotic function. Genes Dev 12:1975-85
Sakamuro, D; Sabbatini, P; White, E et al. (1997) The polyproline region of p53 is required to activate apoptosis but not growth arrest. Oncogene 15:887-98

Showing the most recent 10 out of 21 publications