Apoptosis antagonizing transcription factor AATF is a novel coactivator of nuclear hormone receptors

Apoptosis antagonizing transcription factor AATF was identified as interaction partner of Dlk/ZIP kinase and shown to exhibit transactivation activity in Gal4‐based reporter gene expression assays. The human ortholog Che‐1 was independently isolated as interacting protein of RNA polymerase II suggesting that AATF might be a transcriptional adapter or mediator which serves to link transcriptional activators to the general transcription machinery. Consistent with this assumption, AATF contains several interaction motifs including a leucine zipper and three putative binding motifs for nuclear hormone receptors. In this study, we investigated a possible functional relationship of AATF to nuclear receptors. Indeed, AATF enhanced transactivation by several steroid hormone receptors including androgen, estrogen and glucocorticoid receptors in a hormone‐dependent manner. This enhancing effect was further increased by p300 but not by a mutant of p300 lacking acetyl transferase activity. AATF bound directly to the receptors in vitro. Co‐activation was impaired with AATF mutants bearing mutations in the LXXLL NR binding motifs. Our data suggest that AATF is a novel coactivator of nuclear hormone receptors.