Evolution of the nuclear receptor gene superfamily.

Abstract

Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid hormone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (ii) the vitamin D and ecdysone receptors, as well as the FTZ‐F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place.

Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival

“…The AR, together with the receptors of glucocorticoid, progesterone and mineralocorticoid, are closely related members (class I) in the nuclear receptor superfamily. 22 They all recognize similar response elements (steroid response element, SRE), which are organized as inverted repeats of 5 0 -TGTTCT-3 0 -like sequences with a threenucleotide spacer. 23 We and others have shown that SGK-1 expression is regulated by glucocorticoid via an imperfect glucocorticoid response element (GRE) on the sgk1 promoter.…”

“…Reporter gene assay showed that the promoter fragment containing this GRE motif was activated by androgen treatment at AR-dependent manner in LNCaP cells that are null of glucocorticoid receptor (GR). 35 Because the AR and the GR are closely related members in the steroid hormone receptor family, 22 it is plausible that this GRE (termed as ARE-1) motif is involved in androgen-induced SGK-1 expression.…”

NOR‐2 (neuron‐derived orphan receptor), a brain zinc finger protein, is highly induced during liver regeneration

“…Indeed, NOR-2 contains two zinc-fingers of the C2C2 type, as do of the members of this family [16]. While we finished the sequencing of NOR-2, a second computer analysis showed that this factor was identical, from ATG (at 487 nt) until 1,746 nt, to NOR-1 which has been very recently identified [10].…”

Rel/NF-κB transcription factors and IκB inhibitors: Evolution from a unique common ancestor

“…Our analysis revealed that the pattern of gene duplication events that explain the present diversity of Rel/NF-kB and IkB families is very similar to what happened for other transcription factor families. We previously demonstrated that the diversity of ETS genes and nuclear receptors, as for the Hox/HOM or Myc families, arises very early during metazoan evolution and then increases speci®cally in the vertebrate lineage (Atchley and Fitch, 1995;Holland and Garcia-Fernandez, 1996;Laudet et al, 1992Laudet et al, , 1993. Likewise, the existence of paralogous members such as c-Rel, RelA and RelB or NF-kB1 and NF-kB2, shows that the diversity of Rel/NF-kB or IkB families members was also increased during the vertebrate evolution.…”