NUCLEAR RECEPTORS - STRUCTURE, FUNCTION AND INVOLVEMENT IN DISEASE

Nuclear hormone receptors are acting as transcription factors in the c ell nucleus, They regulate gene expression of hormonal regulated targe t genes, The role of hormone in the transcriptional process is to modu late and change the nuclear receptor functionality, Receptors contain a DNA binding domain that enables them to bind to hormone response ele ments of target genes, Nuclear hormone receptors bind to lipophilic ho rmones produced by the organisms' endocrine system, which links the se cretion of hormones directly to regulation of gene expression of respo nsive tissues, In recent years increasing numbers of naturally occurin g mutations of a variety of nuclear hormone receptor genes were identi fied in patients showing abnormalities in hormonal response, Here, we present an overview of nuclear receptors and their mutant forms which cause human syndromes or are associated,vith cancer progression, The m ajor scope of this article is to give an overview on the structural-fu nctional relationship and based on that, to understand the effects of naturally occuring receptor mutants on the molecular level, Thereby, f unctional aberrations of naturally occuring receptors for androgen, gl ucocorticoids, mineralocorticoid, estrogen, vitamin D3, retinoic acid, and thyroid hormone as well as the orphan receptor DAX1 are discussed . (C) 1997 Elsevier Science Ltd. All rights reserved.