Differences in the interactions of oncogenic adenovirus 12 early region 1A and nononcogenic adenovirus 2 early region 1A with the cellular coactivators p300 and CBP.
Association with the cellular coactivators p300 and CBP is required for the growth-regulatory function of adenoviral (Ad) early region 1A (E1A) proteins. E1A regions necessary for these interactions overlap with domains involved in the induction of tumours in immunocompetent rodents through highly oncogenic Ad12. Differences in the association of cellular factors with the respective E1A domains of Ad12 and nononcogenic Ad2 might therefore be involved in serotype-specific oncogenicity. We analyzed the interaction of the Ad12 E1A 235R protein with p300 and CBP. Here we demonstrate that in the case of Ad12, but not Ad2/5, amino acids (aa) 1-29 of E1A proteins are sufficient to bind the p300-C/H3 domain in vivo and wild-type p300 in vitro. The conserved arginine-2, which is essential for the interaction between Ad2 E1A and p300, was dispensable for the Ad12 E1A 235R-p300 interaction in vitro. In addition to the p300-C/H3 region, we identified a second domain within p300 (aa 1999-2200) binding to the 235R protein. Contrary to p300, the amino-terminus and CR1 are necessary to associate with CBP. The aa 1-29 of the 235R protein but not CR1 are essential for the repression of colTRE-driven gene expression. This repression function is strictly dependent on p300 but not on CBP.
Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Hefelandstrasse 55, 45122 Essen, Germany.
K S
KS
Lipinski
P
P
Fax
B
B
Wilker
H
H
Hennemann
D
D
Brockmann
H
H
Esche
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D050882:CREB-Binding Protein; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human