Abstract
Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary- steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG→GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.
| Original language | English |
|---|---|
| Pages (from-to) | 987-994 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 311 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 28 2003 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Functional characterization of a new human Ad4BP/SF-1 variation, G146A. / WuQiang, Fan; Yanase, Toshihiko; Wei, Liu; Oba, Koichi; Nomura, Masatoshi; Okabe, Taijiro; Goto, Kiminobu; Nawata, Hajime.
In: Biochemical and Biophysical Research Communications, Vol. 311, No. 4, 28.11.2003, p. 987-994.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional characterization of a new human Ad4BP/SF-1 variation, G146A
AU - WuQiang, Fan
AU - Yanase, Toshihiko
AU - Wei, Liu
AU - Oba, Koichi
AU - Nomura, Masatoshi
AU - Okabe, Taijiro
AU - Goto, Kiminobu
AU - Nawata, Hajime
PY - 2003/11/28
Y1 - 2003/11/28
N2 - Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary- steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG→GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.
AB - Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary- steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG→GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.
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UR - http://www.scopus.com/inward/citedby.url?scp=0242606222&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2003.10.096
DO - 10.1016/j.bbrc.2003.10.096
M3 - Article
C2 - 14623279
AN - SCOPUS:0242606222
VL - 311
SP - 987
EP - 994
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -