Role of p300-family proteins in E1A oncogene induction of cytolytic susceptibility and tumor cell rejection

AUTOR(ES)

Cook, James L.

FONTE

The National Academy of Sciences of the USA

RESUMO

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.

Documentos Relacionados

• E1A oncogene induction of cytolytic susceptibility eliminates sarcoma cell tumorigenicity.
• Induction of susceptibility to tumor necrosis factor by E1A is dependent on binding to either p300 or p105-Rb and induction of DNA synthesis.
• p300 binding by E1A cosegregates with p53 induction but is dispensable for apoptosis.
• Functional importance of complex formation between the retinoblastoma tumor suppressor family and adenovirus E1A proteins as determined by mutational analysis of E1A conserved region 2.
• Differential induction of cytolytic susceptibility by E1A, myc, and ras oncogenes in immortalized cells.