Transcription Activation by Nuclear Receptors

Abstract

Nuclear receptors constitute a superfamily of ligand-inducible transcription factors which respond to endocrine, paracrine and, possibly, autocrine signals. Multiple regulatory mechanisms assure that signal transduction results in an accurate regulation of the respective gene networks. Apart from selective expression of the cognate receptor and its binding to specific hormone response elements of target genes, additional mechanisms are responsible for the cell- and promoter-specific transcription activation. They are based on the “interpretation” of the signal by the multiple functional modules of a given receptor and involve a specific interplay with various factors binding to complex target gene promoters and cell-specific intermediary transcription factors that mediate the activity of the two receptor transcription activation functions, as well as homo- and heterodimerization, and interference with other signalling pathways. Moreover, a single ligand may initiate different gene programs due to the differential target gene specificities of nuclear receptor isoforms. Thus, signal transduction by nuclear receptors involves a multitude of interactive elements, as could have been expected from the central role of these signals in homeostasis, embryonic development and differentiation. Two distinct mechanisms are involved in anti-hormone action. Type I anti-hormones impair the activity of the transcription activation function, while type II antagonists impair DNA binding. Experiments aimed at an understanding of these mechanisms are discussed.