Role of p300-family proteins in E1A oncogene induction of cytolytic susceptibility and tumor cell rejection.
The mechanism by which the adenoviral (Ad) E1A oncogene induces cellular susceptibility to lysis by killer lymphocytes involves interactions between its first exon and different second-exon accessory regions. Mutational analysis showed that two first-exon regions--one in the N terminus and one in the conserved region 1 (CR1) domain--are necessary for this activity. E1A complex formation with cellular p300 protein through these first-exon-encoded regions correlated with induction of the cytolytic susceptible phenotype but was only effective in the context of E1A second-exon expression. An E1A first-exon deletion that prevented p300 binding eliminated both oncoprotein-induced cytolytic susceptibility and rejection of transfected sarcoma cells by immunocompetent animals. These results suggest that the E1A oncogene induces cytolytic susceptibility and tumor rejection by interactions with cellular proteins of the p300 family that affect transcription of genes involved in the cellular response to injury inflicted by host killer cells.
Cook
J L
JL
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Krantz
C K
CK
Routes
B A
BA
D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004252:DNA Mutational Analysis; D050881:E1A-Associated p300 Protein; D004622:Embryo, Mammalian; D005091:Exons; D006084:Graft Rejection; D007668:Kidney; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000276:immunology*; D009857:Oncogenes; D012513:Sarcoma, Experimental / Q000276:immunology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology*; D014162:Transfection
D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse