Anzick et al. (1997) reported the deduced sequence of the 1,420-amino acid
AIB1 polypeptide, and found that AIB1 is a member of the SRC-1 family of nuclear receptor coactivators. AIB1 (for 'amplified in breast
cancer-1') is
amplified and overexpressed in breast and ovarian cancer cell lines as well as in breast cancer biopsies, interacts with
estrogen receptors in a ligand-dependent fashion, and functions to enhance estrogen-dependent transcription.
NCBI Summary:
The protein encoded by this gene is a nuclear receptor coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has histone acetyltransferase activity and recruits p300/CBP-associated factor and CREB binding protein as part of a multisubunit coactivation complex. This protein is initially found in the cytoplasm but is translocated into the nucleus upon phosphorylation. Two transcript variants encoding different isoforms have been found for this gene. In addition, a polymorphic repeat region is found in the C-terminus of the encoded protein.
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Nuclear receptors require coactivators to mediate transcriptional activation of their target genes
. The steroid receptor coactivator (SRC) family consists of three newly
identified coactivators designated SRC-1 , GRIP1 (TIF2/SRC-2) , and p/CIP
(RAC3/ACTR/AIB1/TRAM1/SRC-3) . Results from in vitro analyses suggest that SRCs
mediate transcriptional activation through multiple mechanisms including (i) direct interaction with
ligand-bound nuclear receptors (1); (ii) direct contact with certain general transcription factors such
as TFIIB and TBP ; (iii) interaction with common transcriptional coactivators such as CBP, p300, and p/CAF ; (iv)
interaction with other coactivators such as coactivator-associated arginine methyltransferase 1 (CARM-1), cancer-amplified
transcriptional coactivator ASC-2, PPAR coactivator-1 (PGC-1), and steroid receptor RNA coactivator (SRA) ; (v)
participation in chromatin remodeling through their intrinsic histone acetyltransferase activity ; and (vi) enzymatic
modification of other constituents of the coactivator complex .
Cellular localization
Nuclear
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Jianming Xu,, et al 2000 reported that the steroid receptor coactivator SRC-3
(p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for
normal growth, puberty, female reproductive function,
and mammary gland development.
They
show that mouse SRC-3 is expressed in a tissue-specific fashion and distributed mainly in the oocytes, mammary glands,
olfactory bulb, smooth muscle, hepatocytes, and vaginal epithelium.
Follicle stages
Secondary, Antral, Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment:Jianming Xu,, et al 2000 reported that genetic disruption of SRC-3 in mice
results in a pleiotropic phenotype showing dwarfism, delayed puberty, reduced female reproductive function, and blunted
mammary gland development. Hormonal analysis indicates that SRC-3 plays a role in both the growth hormone regulatory
pathway and the production of estrogen, which may explain the observed phenotypes.
The authors examined the superovulation capability and
oocyte fertility. After treatment with pregnant mare's serum gonadotropin and human chorionic gonadotropin, all wild-type
females were induced to superovulate and gave an average of 23.7 ? 5.5 eggs per mouse . However, only 60% of
SRC-3/ females ovulated under the same hormonal treatment, and only 10.4 ? 3.8 eggs per mouse were produced on average. No mature follicles were observed in the ovaries from those SRC-3/ mice that did
not ovulate (data not shown). When superovulated females were mated to fertile males, ovulated eggs from both wild-type
and null mice showed a similar fertilization rate of 50%.