A novel estrogen receptor-related protein gamma splice variant lacking a DNA binding domain exon modulates transcriptional activity of a moderate range of nuclear receptors.
A novel estrogen receptor-related protein (ERR) gamma splice variant cDNA (ERRgamma3) was found in human full-length cDNA libraries. ERRgamma3 cDNA consists of 3362 base pairs and has an open reading frame of 1188bp. The predicted peptide sequence of ERRgamma3 differs from both ERRgamma1 and ERRgamma2 in missing 39 amino acid residues corresponding to the second zinc finger motif of the DNA binding domain (DBD). ERRgamma3 gene consists of 8 exons including three unique 5'-terminal exons and lacks the exon encoding the second zinc finger motif. The expression of ERRgamma3 was confined to adipocytes and prostate while that of ERRgamma2 was fairly widespread. The ERRgamma3 product was shown by transactivation assay to have no ability to activate ERE-controlled transcription. However, ERRgamma3 has an ability to modulate the transcriptional activity of other nuclear hormone receptors. ERRgamma3 augmented the ligand-dependent transcriptional activities of ER (estrogen receptor) alpha, ERbeta, and thyroid receptor (TR) alpha by 1.3-, 4-, and 2.1-fold whereas it inhibited fully the activity of glucocorticoid receptor (GR). However, ERRgamma3 had no effect on Vitamin D3 receptor, retinoic acid receptor alpha or peroxisome proliferator activated receptor alpha, beta, and gamma. These findings will help to elucidate the physiological role of the ERRgamma subfamily.
Kojo
Hitoshi
H
Advanced Technology Platform Research Laboratory, Fujisawa Pharmaceutical Co. Ltd., Japan. TCC01424@nifty.ne.jp
Tajima
Kaoru
K
Fukagawa
Masao
M
Isogai
Takao
T
Nishimura
Shintaro
S
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C490917:ESRRG protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; C425824:estrogen receptor gamma; D004247:DNA