Accumulation of p53 in response to adenovirus early region 1A sensitises human cells to tumour necrosis factor-alpha induced apoptosis

Xian Zhang, R Hussain, Andrew Turnell, JS Mymryk, Phillip Gallimore, Roger Grand

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Many tumor cells are resistant to tumor necrosis factor alpha (TNF alpha)-induced apoptosis. Adenovirus early region 1A (AdE1A) sensitizes the otherwise resistant cells to TNF alpha AdE1A also stabilizes the p53 protein. The present study demonstrates a correlation between AdE1A-induced sensitization and stabilization of p53 in TNF alpha-induced apoptosis since the N-terminal and CR2 regions, the binding sites for CBP/p300, Rb and 26S proteasome regulatory components, are required for both these actions of AdE1A. TNF alpha does not induce apoptosis and AdE1A fails to sensitize TNF alpha cytotoxicity in p53-negative cells. However, introduction of exogenous p53 overcomes the cellular resistance to TNFa. toxicity and enhances AdE1A sensitization, demonstrating that AdE1A sensitizes TNF alpha-induced apoptosis by its stabilization of p53. A proteasome inhibitor, lactacystin, enhances TNF alpha cytotoxicity in p53-positive and -negative cells, suggesting that accumulation of cellular proteins other than p53 might also regulate the cellular response to TNF alpha signaling. (c) 2005 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)285-295
Number of pages11
JournalVirology
Volume340
DOIs
Publication statusPublished - 30 Sep 2005

Keywords

  • Rb
  • 26S proteasome
  • p53
  • TNF alpha
  • adenovirus
  • apoptosis
  • CBP/p300
  • AdE1A

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