Adenovirus Type 5 Early Region 1B 156R Protein Promotes Cell Transformation Independently of Repression of p53-Stimulated Transcription
- 1 January 2007
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (1), 95-105
- https://doi.org/10.1128/jvi.01608-06
Abstract
Early region 1B (E1B) of adenovirus type 5 (Ad5) encodes at least five different polypeptides generated by alternative splicing of a common mRNA precursor. Two of these gene products, E1B-19K and E1B-55K, are individually capable of cooperating with the Ad5 E1A proteins to completely transform rodent cells in culture. Substantial evidence suggests that these two E1B proteins contribute to cell transformation by antagonizing growth arrest and apoptosis. Here, we performed genetic and biochemical analyses to assess the attributes of the remaining E1B proteins (E1B-156R, E1B-93R, and E1B-84R). Our results show that E1B-156R, which comprises the 79 amino-terminal and 77 carboxy-terminal amino acids of E1B-55K, also enhances focal transformation of primary rat cells in cooperation with E1A. Since E1B-156R seemed unable to relocalize p53 and inhibit its transactivating function, it must be assumed that it contributes to transformation independently of repression of p53-stimulated transcription. Furthermore, we discovered that E1B-156R contains a functional transcriptional repression domain and binds Ad5 E4orf6 and the cellular apoptosis regulator Daxx. While the ability to bind E4orf6 could indicate further biological functions of E1B-156R in viral infection, the interaction with Daxx might also be linked to its transforming potential. Taken together, these analyses introduce E1B-156R as a novel transformation-promoting E1B protein that acts without repressing p53 transactivation. Moreover, identification of the interaction partners E4orf6 and Daxx provides a first glance of E1B-156R's potential functions.Keywords
This publication has 61 references indexed in Scilit:
- Recent lessons in gene expression, cell cycle control, and cell biology from adenovirusOncogene, 2005
- Adenovirus E1B 55-Kilodalton Oncoprotein Binds to Daxxand Eliminates Enhancement of p53-Dependent Transcription byDaxxJournal of Virology, 2003
- The Interaction of Pax5 (BSAP) with Daxx Can Result in Transcriptional Activation in B CellsJournal of Biological Chemistry, 2002
- “Hit-and-Run” Transformation by Adenovirus OncogenesJournal of Virology, 2001
- Consequences of disruption of the interaction between p53 and the larger adenovirus early region 1B protein in adenovirus E1 transformed human cellsOncogene, 2000
- The 2.2 kb E1b mRNA of human Ad12 and Ad5 codes for two tumor antigens starting at different AUG tripletsCell, 1981
- Control of messenger RNA concentration by differential cytoplasmic half-lifeJournal of Molecular Biology, 1981
- Complex splicing patterns of RNAs from the early regions of adenovirus-2Journal of Molecular Biology, 1979
- Structure of two spliced mRNAs from the transforming region of human subgroup C adenovirusesNature, 1979
- Regulation of the appearance of cytoplasmic RNAs from region 1 of the adenovirus 2 genomeJournal of Molecular Biology, 1978