title: E1A is sufficient by itself to induce apoptosis independent of p53 and other adenoviral gene products.
abstract: Induction of apoptosis seems to be a key function in maintaining normal cell growth by exerting negative controls on cell proliferation and suppressing tumorigenesis. The adenovirus E1A oncogene shows both cell cycle progression and apoptotic functions. To understand the mechanism of E1A-induced apoptosis, the apoptotic function of E1A 13S was investigated in p53-null cells. We show here that E1A is sufficient by itself to induce substantial apoptosis independent of p53 and other adenoviral genes. The apoptotic function of E1A is accompanied by processing of caspase-3 and cleavage of poly(ADP-ribose)-polymerase. Cell death is significantly blocked by the caspase inhibitor zVAD-fmk and when coexpressed with E1B19K, Bcl-2 or the retinoblastoma protein (RB). Analyses of E1A mutants indicated that the apoptotic activity of E1A correlates closely with the ability to bind the key regulators of E2F1-induced apoptosis, p300 and RB. Finally, in vivo relevance of down-modulation of p53-independent apoptosis for efficient transformation is demonstrated.
authors.affiliation: Institute of Molecular Biology (Cancer Research), University of Essen, Medical School, Hufelandstr. 55, 45122 Essen, Germany. brigitte.puetzer@uni-essen.de
authors.forename: B M
authors.initials: BM
authors.lastname: Pützer
authors.forename: T
authors.initials: T
authors.lastname: Stiewe
authors.forename: K
authors.initials: K
authors.lastname: Parssanedjad
authors.forename: S
authors.initials: S
authors.lastname: Rega
authors.forename: H
authors.initials: H
authors.lastname: Esche
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D017500:Adenovirus E1A Proteins; D016159:Tumor Suppressor Protein p53