The E1A products of oncogenic adenovirus serotype 12 include amino-terminally modified forms able to bind the retinoblastoma protein but not p300

Abstract

The cell growth-regulating properties of the adenovirus type 5 (Ad5) E1A oncogene correlate closely with the binding of the E1A products to specific cellular proteins. These proteins include the products of the retinoblastoma tumor susceptibility gene and a 300-kDa product, p300. pRB binds to E1A sequences that are highly conserved among the E1A products of various serotypes, while p300 binding requires sequences in the E1A amino terminus, a region that is not highly conserved. To help evaluate the roles of the E1A-associated proteins in cell growth control, we have compared the p300-binding abilities of the E1A products of Ad5 and of the more oncogenic Ad12 serotype. We show here that despite encoding a sequence that varies somewhat from the p300-binding sequences of Ad5 E1A, the Ad12 E1A products associate with p300 with an affinity similar to that of the Ad5 E1A products. Both the 12S and 13S splice products of Ad12 E1A, like those of Ad5 E1A, encode proteins able to associate with p300. Interestingly, though, both also give rise to prominent forms that are amino terminally modified and unable to associate with p300. This modification, at least in the 13S product, does not appear to diminish the affinity of this product for the retinoblastoma protein.