Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3.

The adenovirus (Ad) E1A proteins alter the expression level and activity of AP-1/ATF transcription factors. Previously we have shown that in AdE1-transformed cells cJun is hyperphosphorylated in its N-terminal transactivation domain, which parallels enhanced transactivation function. To find out whether the interaction between cJun and other cellular proteins is altered, we have searched for proteins which would physically associate with cJun. In this report we show that in AdE1-transformed cells cJun specifically associates with two proteins of 21 and 23 kD. These proteins are not expressed at detectable levels in the parental cells or in cells transformed by oncogenes other than AdE1. The cJun-associated proteins represent different forms of the bZIP transcription factor ATF3, the human homolog of rat LRF1. The expression of ATF3 is induced in AdE1-transformed cells and is a direct effect of the expression of E1A. Through induction of ATF3 expression and the subsequent formation of cJun/ATF3 heterodimers, E1A alters the repertoire of AP-1/ATF factors and may thereby redirect the corresponding gene-expression program. Since the induction of ATF3 is a function of sequences within the transforming 12S-ElA protein, cJun/ATF3 complexes might be involved in establishing cellular transformation by AdE1A.