The transcription intermediary factor 1β coactivates the androgen receptor

Abstract

The androgen receptor (AR) is a ligand-inducible transcription factor. Its transcription activation domain consists of the two transcription activation units called Tau-1 and Tau- 5. Tau-5 interacts with p160 coactivators like the transcription intermediary factor 2 (TIF2), which in their turn recruit histone modifiers and chromatin-remodelling complexes. The mechanism of action of Tau-1, however, remains elusive. Here, we demonstrate that transcription intermediary factor 1β (TIF1β) can induce the activity of the AR up to five fold when tested in vitro. Although there is no evidence for direct interactions between TIF1β and AR, mutation studies show that the activity of TIF1β depends on the integrity of Tau-1 in AR on the one hand, and the so-called tripartite motif domain in TIF1β on the other. Surprisingly, the coactivation by TIF1β via Tau-1 seems additive rather than cooperative with the AR coactivation by TIF2. Some mutations naturally occurring in androgen-insensitivity syndrome patients that reside in Tau-1 seem to impair the TIF1β coactivation of the AR, indicating that TIF1β could also be relevant for the in vivo androgen response in humans. Moreover, since TIF1β is well expressed in prostate cancer cells, its functional interaction with androgen signalling could in the long run be a therapeutic target for this disease.