Overview of the structural basis for transcription regulation by nuclear hormone receptors

Essays in Biochemistry
Raj KumarE Brad Thompson

Abstract

The mechanism of action of the nuclear hormone receptors (NHRs) as gene- regulatory molecules has become a major focus of current biological interest. NHRs belong to the superfamily of ligand-activated transcription factors, which are involved in the regulation of homoeostasis, reproduction, development and differentiation. To fully understand their functions, it is important to know the functional three-dimensional structure of these proteins. Molecular cloning and structure-function analyses have revealed that NHRs commonly have three functional regions: the N-terminal, DNA-binding and ligand-binding domains. Structures of some of these domains expressed independently have been solved. However, to date the three-dimensional structure remains unknown for full-length and even for any two domains together of any NHR family member. The available structures nevertheless begin to give clues of how site-specific DNA binding takes place, and how ligand binding alters the ligand-binding domain, consequently affecting potential interactions of the NHRs with co-activators/co-repressors and other components of basal transcriptional machinery. However, precisely how signals from a ligand through its NHR are passed to specific genes is sti...Continue Reading

Citations

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