The activation domain of a basic helix-loop-helix protein is masked by repressor interaction with domains distinct from that required for transcription regulation.

Abstract

While there are many examples of protein-protein interactions modulating the DNA-binding activity of transcription factors, little is known of the molecular mechanisms underlying the regulation of the transcription activation function. Using a tuo-hybrid system we show here that transcription repression of the basic domain/ helix-loop-helix factor PH04 is mediated by complex formation with the PH080 repressor. In contrast to other systems, such as inhibition of GAL4 by GAL80 or of p53 by MDM2, where repression is mediated by direct interaction at regions overlapping the transcription activation domain, interaction with PH080 involves two regions of PH04 distinct from those involved in transcription activation or DNA-binding and dimerization. The possibility that repression of PH04 by PH080 may represent a general mechanism of transcription control, including regulation of the cell-type-specific transcription activation domain of c-Jun, is discussed.