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Adenovirus 2 E1B-55K protein relieves p53-mediated transcriptional repression of the survivin and MAP4 promoters.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2003 (English)In: FEBS Letters, ISSN 0014-5793, Vol. 552, no 2-3, 214-218 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 552, no 2-3, 214-218 p.
Identifiers
URN: urn:nbn:se:uu:diva-91175OAI: oai:DiVA.org:uu-91175DiVA: diva2:163817
Available from: 2003-12-22 Created: 2003-12-22 Last updated: 2011-06-30Bibliographically approved
In thesis
1. The Interaction of the Adenovirus E1B-55K Protein with a Histone Deacetylase Complex: Its Importance in Regulation of P53 Protein Functions
Open this publication in new window or tab >>The Interaction of the Adenovirus E1B-55K Protein with a Histone Deacetylase Complex: Its Importance in Regulation of P53 Protein Functions
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The human tumour suppressor protein p53 is an effective inhibitor of cell growth, by inducing cell cycle arrest and apoptosis. However, p53-induced cell growth inhibition can be detrimental for virus multiplication. Therefore, viruses encode for proteins, which can interfere with the functions of the p53 protein. Human adenoviruses encode for a transcription repressor protein named E1B-55K, which inhibits the activity of the p53 protein during a lytic adenovirus infection.

In this thesis, we have studied the biochemical characteristics of the E1B-55K protein and how the E1B-55K protein interferes with the function of p53 as a transcription factor.

Our data show that the E1B-55K protein interacts with the Sin3 co-repressor complex in adenovirus transformed and in adenovirus infected cells. Furthermore, the E1B-55K protein recruites a histone deacetylase activity, indicating that the E1B-55K protein is associated with a functional chromatin modifying complex. We also show that in addition to repressing p53-activated transcription, E1B-55K could also relieve p53-mediated repression of the survivin and Map4 promoters.

Previous results have shown that E1B-55K inhibits p53 as a transcriptional activator of the p21/CDKN1A promoter. Here we show that the E1B-55K protein prevents p53 from inducing histone H3 and H4 acetylation on p21/CDKN1A promoter, which coincided with the inhibition of p21/CDKN1A protein expression. Notably, the Sin3 complex was detected in the vicinity of the p53 binding site on the p21/CDKN1A promoter, suggesting that the E1B-55K protein blocked p53-mediated histone acetylation by recruitment of a histone deacetylase activity. Inhibition of p21/CDKN1A protein expression might be the reason, why the E1B-55K protein alleviates p53-dependent transcriptional repression of the survivin promoter.

Finally, we show that oligomerisation of the E1B-55K protein is important for the defined subcellular localization of the protein and for its function as a repressor of p53-activated transcription.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 62 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1314
Keyword
Biochemistry, adenovirus, E1B-55K, p53, histone acetylation, Sin3, Biokemi
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-3887 (URN)91-554-5829-7 (ISBN)
Public defence
2004-01-30, C10-305, BMC, Husargatan3, BMC, 75123, Uppsala, 09:15
Opponent
Supervisors
Available from: 2003-12-22 Created: 2003-12-22Bibliographically approved

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