ALTERED AP-1 ATF COMPLEXES IN ADENOVIRUS-E1-TRANSFORMED CELLS DUE TO E1A-DEPENDENT INDUCTION OF ATF3/

The adenovirus (Ad) E1A proteins alter the expression level and activi ty 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 funct ion. To find out whether the interaction between cJun and other cellul ar proteins is altered, we have searched for proteins which would phys ically associate with cJun. In this report we show that in AdE1-transf ormed cells cJun specifically associates with two proteins of 21 and 2 3 kD. These proteins are not expressed at detectable levels in the par ental cells or in cells transformed by oncogenes other than AdE1. The cJun-associated proteins represent different forms of the bZIP transcr iption factor ATF3, the human homolog of rat LRF1. The expression of A TF3 is induced in AdE1-transformed cells and is a direct effect of the expression of E1A. Through induction of ATF3 expression and the subse quent formation of cJun/ATF3 heterodimers, E1A alters the repertoire o f AP-1/ATF factors and may thereby redirect the corresponding gene-exp ression program. Since the induction of ATF3 is a function of sequence s within the transforming 12S-E1A protein, cJun/ATF3 complexes might b e involved in establishing cellular transformation by AdE1A.