Review on NCOA3 (nuclear receptor coactivator 3), with data on DNA, on the protein encoded, and where the gene is implicated

Anzick, SL

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Gene Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(3)  
 
214 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
NCOA3 (Nuclear Receptor Coactivator 3) 
Sarah L Anzick 
Cancer Genetics Branch National Human Genome, Research Institute National Institutes of Health 50 South 
Drive, MSC 8000 Bldg. 50, Rm. 5148 Bethesda, MD 20892-8000, USA (SLA) 
Published in Atlas Database: April 2005 
Online updated version: http://AtlasGeneticsOncology.org/Genes/NCOA3ID505ch20q13.html 
DOI: 10.4267/2042/38207 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2005 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Other names: AIB1 (amplified in breast cancer-1); 
ACTR; RAC3 (RAR-associated coactivator 3); SRC3 
(steroid receptor coactivator protein 3); TRAM-1 
(thyroid hormone receptor activator molecule 1); pCIP 
(p300/CBP-integrator associated protein; mouse) 
HGNC (Hugo): NCOA3 
Location: 20q13.1 
DNA/RNA 
Description 
The human AIB1 gene spans approximately155 kb and 
has 23 exons.  
RNA Expression: Highly expressed in placenta, heart, 
pancreas, muscle, brain, liver, uterus, pituitary, 
mammary gland, and testis. Lower levels of expression 
are found in lung and kidney. 
Transcription 
Transcription is from centromere to telomere. There are 
two reported transcripts: Isoform a (7935 bp) and 
isoform b (7923 bp). Isoform b uses an alternate in-
frame splice site and lacks exon 3. 
 
 
 
AIB1 (20q12) 
 
 
Genomic structure of NCOA3 with NCBI Build 35.1 genomic positions indicated. Black boxes indicate exons. The translational start (*) 
and stop codons (^) are also shown. UTR, untranslated region. 
 
 
NCOA3 (Nuclear Receptor Coactivator 3) Anzick SL 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(3)  
 
215 
Pseudogene 
Chromosome 8 (AF010227). 
Protein 
Description 
A member of the p160/steroid receptor coactivator 
family. 1424 amino acids. 155 kDa (130 kDa encoded 
by isoform b). 
Expression 
Protein expression found in testis, lung, liver, brain, 
mammary gland, and heart. 
Localisation 
Mainly cytoplasmic and weakly nuclear. The protein 
translocates to the nucleus upon TNF activation and 
phosphorylation. 
Function 
A transcriptional coactivator that interacts with nuclear 
hormone receptors to enhance their transcriptional 
activation. AIB1 interacts with other transcription 
factors including TP52, NfkB, and ER81. It has 
intrinsic histone acytyltransferase activity and recruits 
CREB Binding Protein (CBP)/p300 cointegrators to a 
multisubunit coactivator complete. 
 
 
 
Mutations 
Somatic 
The gene copy number and expression levels are 
altered in several cancer types. Overexpression has 
been found in breast, ovarian, endometrial, gastric, and 
pancreatic cancers. Amplification of AIB1 in 
hepatocellular carcinoma is associated with poor 
prognosis. Increased numbers of polyglutamine repeats 
correlate with higher breast cancer risk in BRCA1 and 
BRCA2 mutation carriers. However, the polymorphic 
repeat genotype does not influence postmenopausal 
breast cancer risk among Caucasian women in the 
general population. 
To be noted 
Note 
Overexpression of AIB1 in tamoxifen-treated patients 
is associated with tamoxifen resistance and worse 
survival. Tamoxifen behaves as estrogen in breast 
cancer cells that express high levels of AIB1 and 
HER2, resulting in de novo resistance. 
An N-terminally deleted isoform (AIB1-Delta3) which 
lacks exon 3 was identified and found to be 
overexpressed in breast cancer cell lines and in tumors 
from breast cancer patients. Of interest, this splice 
variant has more potent transcriptional coactivation 
properties on estrogen and progesterone receptors than 
the full-length AIB1 protein. 
 
Structural features of AIB1. AIB1 contains a basic helix-loop-helix preceding a PAS (Per/Arnt/Sim) region, serine-and threonine-rich 
regions, and a charged cluster.  There is also a glutamine-rich region that contains a polyglutamine tract. The central portion of the 
protein contains three LXXLL motifs (L=leucine, X=any amino acid) that are critical for interaction with ligand-bound nuclear receptors. An 
activation domain located C-terminal to the nuclear receptor interaction domain contains three LXXLL motifs that are important for 
interaction with general transcription cointegrators, CREB binding protein (CBP)/p300. A second transcriptional activation domain is 
responsible for interaction with histone methyltransferases, coactivator-associated arginine methyltranserase 1 (CARM1) and PRMT1. 
 
References 
Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, 
Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS. 
AIB1, a steroid receptor coactivator amplified in breast and 
ovarian cancer. Science. 1997 Aug 15;277(5328):965-8 
Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, 
Privalsky ML, Nakatani Y, Evans RM. Nuclear receptor 
coactivator ACTR is a novel histone acetyltransferase and 
forms a multimeric activation complex with P/CAF and 
CBP/p300. Cell. 1997 Aug 8;90(3):569-80 
NCOA3 (Nuclear Receptor Coactivator 3) Anzick SL 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(3)  
 
216 
Li H, Gomes PJ, Chen JD. RAC3, a steroid/nuclear receptor-
associated coactivator that is related to SRC-1 and TIF2. Proc 
Natl Acad Sci U S A. 1997 Aug 5;94(16):8479-84 
Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW. 
TRAM-1, A novel 160-kDa thyroid hormone receptor activator 
molecule, exhibits distinct properties from steroid receptor 
coactivator-1. J Biol Chem. 1997 Oct 31;272(44):27629-34 
Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass 
CK, Rosenfeld MG. The transcriptional co-activator p/CIP 
binds CBP and mediates nuclear-receptor function. Nature. 
1997 Jun 12;387(6634):677-84 
Bautista S, Vallès H, Walker RL, Anzick S, Zeillinger R, Meltzer 
P, Theillet C. In breast cancer, amplification of the steroid 
receptor coactivator gene AIB1 is correlated with estrogen and 
progesterone receptor positivity. Clin Cancer Res. 1998 
Dec;4(12):2925-9 
Li H, Chen JD. The receptor-associated coactivator 3 activates 
transcription through CREB-binding protein recruitment and 
autoregulation. J Biol Chem. 1998 Mar 6;273(10):5948-54 
Suen CS, Berrodin TJ, Mastroeni R, Cheskis BJ, Lyttle CR, 
Frail DE. A transcriptional coactivator, steroid receptor 
coactivator-3, selectively augments steroid receptor 
transcriptional activity. J Biol Chem. 1998 Oct 
16;273(42):27645-53 
Ghadimi BM, Schröck E, Walker RL, Wangsa D, Jauho A, 
Meltzer PS, Ried T. Specific chromosomal aberrations and 
amplification of the AIB1 nuclear receptor coactivator gene in 
pancreatic carcinomas. Am J Pathol. 1999 Feb;154(2):525-36 
Lee SK, Kim HJ, Kim JW, Lee JW. Steroid receptor 
coactivator-1 and its family members differentially regulate 
transactivation by the tumor suppressor protein p53. Mol 
Endocrinol. 1999 Nov;13(11):1924-33 
Haiman CA, Hankinson SE, Spiegelman D, Colditz GA, Willett 
WC, Speizer FE, Brown M, Hunter DJ. Polymorphic repeat in 
AIB1 does not alter breast cancer risk. Breast Cancer Res. 
2000;2(5):378-85 
Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, 
Masuda K, Kimura A, Nakamura Y, Inazawa J, Abe T, 
Yamagishi H. Amplification and over-expression of the AIB1 
nuclear receptor co-activator gene in primary gastric cancers. 
Int J Cancer. 2000 May 20;89(3):217-23 
Werbajh S, Nojek I, Lanz R, Costas MA. RAC-3 is a NF-kappa 
B coactivator. FEBS Lett. 2000 Nov 24;485(2-3):195-9 
Xu J, Liao L, Ning G, Yoshida-Komiya H, Deng C, O'Malley 
BW. 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. Proc Natl Acad Sci U S A. 2000 Jun 
6;97(12):6379-84 
Glaeser M, Floetotto T, Hanstein B, Beckmann MW, 
Niederacher D. Gene amplification and expression of the 
steroid receptor coactivator SRC3 (AIB1) in sporadic breast 
and endometrial carcinomas. Horm Metab Res. 2001 
Mar;33(3):121-6 
Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen 
SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D, 
Garber JE, Lynch HT, Weber BL, Brown M. Modification of 
BRCA1- and BRCA2-associated breast cancer risk by AIB1 
genotype and reproductive history. Cancer Res. 2001 Jul 
15;61(14):5420-4 
Reiter R, Wellstein A, Riegel AT. An isoform of the coactivator 
AIB1 that increases hormone and growth factor sensitivity is 
overexpressed in breast cancer. J Biol Chem. 2001 Oct 
26;276(43):39736-41 
Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ, Guan XY. 
Prognostic significance of c-myc and AIB1 amplification in 
hepatocellular carcinoma. A broad survey using high-
throughput tissue microarray. Cancer. 2002 Dec 
1;95(11):2346-52 
Watanabe T, Imoto I, Katahira T, Hirasawa A, Ishiwata I, Emi 
M, Takayama M, Sato A, Inazawa J. Differentially regulated 
genes as putative targets of amplifications at 20q in ovarian 
cancers. Jpn J Cancer Res. 2002 Oct;93(10):1114-22 
Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, 
O'Malley BW. Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-
3/TRAM-1) Coactivator activity by I kappa B kinase. Mol Cell 
Biol. 2002 May;22(10):3549-61 
Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck 
SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R. Role of 
the estrogen receptor coactivator AIB1 (SRC-3) and HER-
2/neu in tamoxifen resistance in breast cancer. J Natl Cancer 
Inst. 2003 Mar 5;95(5):353-61 
Goel A, Janknecht R. Concerted activation of ETS protein 
ER81 by p160 coactivators, the acetyltransferase p300 and the 
receptor tyrosine kinase HER2/Neu. J Biol Chem. 2004 Apr 
9;279(15):14909-16 
Henke RT, Haddad BR, Kim SE, Rone JD, Mani A, Jessup JM, 
Wellstein A, Maitra A, Riegel AT. Overexpression of the 
nuclear receptor coactivator AIB1 (SRC-3) during progression 
of pancreatic adenocarcinoma. Clin Cancer Res. 2004 Sep 
15;10(18 Pt 1):6134-42 
Kadouri L, Kote-Jarai Z, Easton DF, Hubert A, Hamoudi R, 
Glaser B, Abeliovich D, Peretz T, Eeles RA. Polyglutamine 
repeat length in the AIB1 gene modifies breast cancer 
susceptibility in BRCA1 carriers. Int J Cancer. 2004 Jan 
20;108(3):399-403 
Wu RC, Qin J, Yi P, Wong J, Tsai SY, Tsai MJ, O'Malley BW. 
Selective phosphorylations of the SRC-3/AIB1 coactivator 
integrate genomic reponses to multiple cellular signaling 
pathways. Mol Cell. 2004 Sep 24;15(6):937-49 
This article should be referenced as such: 
Anzick SL. NCOA3 (Nuclear Receptor Coactivator 3). Atlas 
Genet Cytogenet Oncol Haematol. 2005; 9(3):214-216. 


NCOA3 (nuclear receptor coactivator 3)

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NCOA3 (nuclear receptor coactivator 3)

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