The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha

White, E., Sabbatini, P., Debbas, M., Wold, W. S., Kusher, D. I., Gooding, L. R. (June 1992) The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol, 12 (6). pp. 2570-80. ISSN 0270-7306 (Print)0270-7306 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1317006
DOI: 10.1128/MCB.12.6.2570

Abstract

The adenovirus E1A and E1B proteins are required for transformation of primary rodent cells. When expressed in the absence of the 19,000-dalton (19K) E1B protein, however, the E1A proteins are acutely cytotoxic and induce host cell chromosomal DNA fragmentation and cytolysis, analogous to cells undergoing programmed cell death (apoptosis). E1A alone can efficiently initiate the formation of foci which subsequently undergo abortive transformation whereby stimulation of cell growth is counteracted by continual cell death. Cell lines with an immortalized growth potential eventually arise with low frequency. Coexpression of the E1B 19K protein with E1A is sufficient to overcome abortive transformation to produce high-frequency transformation. Like E1A, the tumoricidal cytokine tumor necrosis factor alpha (TNF-alpha) evokes a programmed cell death response in many tumor cell lines by inducing DNA fragmentation and cytolysis. Expression of the E1B 19K protein by viral infection, by transient expression, or in transformed cells completely and specifically blocks this TNF-alpha-induced DNA fragmentation and cell death. Cosegregation of 19K protein transforming activity with protection from TNF-alpha-mediated cytolysis demonstrates that both activities are likely the consequence of the same function of the protein. Therefore, we propose that by suppressing an intrinsic cell death mechanism activated by TNF-alpha or E1A, the E1B 19K protein enhances the transforming activity of E1A and enables adenovirus to evade TNF-alpha-dependent immune surveillance.

Item Type: Paper
Uncontrolled Keywords: Adenovirus Early Proteins Adenoviruses, Human/*physiology Animals *Cell Death *Cell Transformation, Viral Cricetinae Cytopathogenic Effect, Viral Down-Regulation HeLa Cells Humans In Vitro Techniques Oncogene Proteins, Viral/*physiology Receptors, Cell Surface/metabolism Receptors, Tumor Necrosis Factor Tumor Necrosis Factor-alpha/*antagonists & inhibitors
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > tumor necrosis factor
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: June 1992
Date Deposited: 23 Sep 2015 20:45
Last Modified: 23 Sep 2015 20:45
PMCID: PMC364450
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31825

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