Orphan Nuclear Receptors

The nuclear receptor superfamily consists of a class of transcription factors comprising more than 100 different proteins. In contrast to membrane-bound receptors, the nuclear receptors are intracellular and act by controlling the activity of genes directly. Most members of this family bind directly to small lipidsoluble signaling molecules, or ligands, which owing to their lipophilic nature can easily enter the target cell. This superfamily includes known receptors for steroid hormones, such as the glucocorticoid receptor (GR), estrogen receptor (ER), progesterone receptor (PR) (see Chapter 20) and nonsteroid hormone receptors such as the vitamin D receptor (VDR), thyroid hormone receptor (TR), retinoic acid receptor (RAR), peroxisome-proliferator activated receptor (PPAR), and retinoid X receptor (RXR), all of which play key roles in animal development, physiology and human disease. The steroid hormones are derived from cholesterol, share a common chemical structural motif, and act in a classic endocrine manner. In contrast, ligands for the nonsteroid receptors are chemically diverse, including vitamin D, thyroid hormone, retinoids, and prostanoids. Furthermore, the source of the ligands for this class of receptors may be either endocrine, or generated intracellularly and not secreted (intracrine), or may be modified within the cell from an apohormone (Fig. 1).

[1]  J. Bar-Tana,et al.  Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4α , 1998, Nature.

[2]  R. Evans,et al.  The RXR heterodimers and orphan receptors , 1995, Cell.

[3]  R. Evans,et al.  Orphan nuclear receptors--new ligands and new possibilities. , 1998, Genes & development.

[4]  V. Giguère,et al.  Orphan nuclear receptor RORα-deficient mice display the cerebellar defects of staggerer , 1998, Mechanisms of Development.

[5]  S. Bandoh,et al.  The NGFI-B subfamily of the nuclear receptor superfamily (review). , 1998, International journal of oncology.

[6]  P. Sigler,et al.  Structural determinants of nuclear receptor assembly on DNA direct repeats , 1995, Nature.

[7]  D. Mangelsdorf,et al.  Nuclear Orphan Receptors: The Search for Novel Ligands and Signaling Pathways , 1998 .

[8]  G. Zhou,et al.  Nuclear receptors have distinct affinities for coactivators: characterization by fluorescence resonance energy transfer. , 1998, Molecular endocrinology.

[9]  A. Monaco,et al.  An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita , 1994, Nature.

[10]  J. Gustafsson,et al.  Orphan nuclear receptors--the first eight years. , 1996, Molecular endocrinology.

[11]  T. Hansen,et al.  Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3) , 1996, Nature.

[12]  M. Tsai,et al.  Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborization. , 1997, Genes & development.

[13]  R. Hammer,et al.  Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXRα , 1998, Cell.