The ATFa proteins, which are members of the CREB/ATF family of transcriptio
n factors, have previously been shown to interact with the adenovirus Ela o
ncoprotein and to mediate its transcriptional activity; they heterodimerize
with Jun, Fos or related transcription factors, possibly altering their DN
A-binding specificity; they also stably bind JNK2, a stress-induced protein
kinase. Here we report the identification acid characterization of a novel
protein isolated in a yeast two-hybrid screen using the N-terminal half of
ATFa as a bait. This 1306-residue protein (mAM, for mouse ATFa-associated
Modulator) is rather acidic (pHi 4.5) and contains high proportions of Ser/
Thr (21%) and Pro (11%) residues. It colocalizes and interacts with ATFa in
mammalian cells, contains a bipartite nuclear localization signal and poss
esses an ATPase activity. Transfection experiments show that mAM is able to
downregulate transcriptional activity, in an ATPase-independent manner. Ou
r results indicate that mAM interacts with several components of the basal
transcription machinery (TFIIE and TFIIH), including RNAPII itself. Togethe
r, these findings suggest that mAM may be involved in the fine-tuning of AT
Fa-regulated gene expression, by interfering with the assembly or stability
of specific preinitiation transcription complexes.