Nuclear receptor coactivator 3
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| Location (UCSC) | Chr 20: 47.5 – 47.66 Mb | Chr 2: 165.99 – 166.07 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene.[5][6] NCOA3 is also frequently called 'amplified in breast 1' (AIB1), steroid receptor coactivator-3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1).
Function
NCOA3 is a transcriptional coactivator protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA3 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA3, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA3 assists nuclear receptors in the upregulation of gene expression.[7][8]
Clinical significance
The ratio of
Several molecular mechanisms implicate NCOA3 (AIB1) in the
PIK3CA (PI3K), activating mutations in the proto-oncogene tyrosine-protein kinase Src, etc.) that lead to persistent activation of ERK and/or PIK3CA/AKT kinase pathways result, in one hand in an enhanced AIB1 transcriptional coactivation capacity,[11] and in the other hand in the inhibition of the proteasome-dependent AIB1 turn-over and therefore, in AIB1 overexpression.[12] In both conditions, the equilibrium of estrogen receptor (ER) complex formation is displaced towards a transcriptionally active complex and thus, counteracting the inhibition caused by anti-estrogenic drugs such as tamoxifen or fulvestrant (selective estrogen receptor modulators
). The result is the restoration of estrogen-sensitive gene transcription and the promotion of cancer progression and/or relapse.
Notably, tumors diagnosed with concomitant overexpression of AIB1 and
HER2/neu have worse outcome with tamoxifen therapy than all other patients combined.[13] In addition, dormant tumor cells of luminal breast cancers treated with endocrine therapy may acquire with time, mutations that alter kinase signalling pathways and ultimately enhance AIB1 oncogenic functions. Also, estrogen receptor-PAX2 complexes repress HER2/neu expression, but loss of PAX2 expression may result in de novo HER2/neu expression and initiate endocrine therapy resistance and relapse.[14]
Interactions
Nuclear receptor coactivator 3 has been shown to
interact
with:
- Androgen receptor,[15][16][17]
- CHUK[18] and
- CREB-binding protein,[18][19]
- DDX17,[20]
- DDX5,[20]
- Estrogen receptor alpha,[20][21][22]
- Estrogen receptor beta,[21][23]
- Glucocorticoid receptor,[24][25]
- IKBKG,[18]
- IKK2,[18]
- Peroxisome proliferator-activated receptor gamma,[26] and
- Retinoid X receptor alpha.[27][28]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000124151 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027678 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9252329.
- PMID 9346901.
- PMID 9252329.
- PMID 9346901.
- ^ "Study sheds new light on tamoxifen resistance". Cordis News. Cordis. 2008-11-13. Archived from the original on 2009-02-20. Retrieved 2008-11-14.
- PMID 19005469.
- PMID 10866661.
- PMID 18593948.
- PMID 12618500.
- PMID 19005469.
- PMID 10965917.
- PMID 11747336.
- PMID 14966121.
- ^ PMID 11971985.
- S2CID 27872061.
- ^ PMID 11250900.
- ^ PMID 11389589.
- PMID 11050174.
- PMID 10681591.
- PMID 12917342.
- PMID 11266503.
- PMID 10944516.
- S2CID 15284825.
- PMID 11851396.
External links
- nuclear receptor coactivator 3 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C91
Further reading
- Liao L, Kuang SQ, Yuan Y, Gonzalez SM, O'Malley BW, Xu J (2003). "Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1". J. Steroid Biochem. Mol. Biol. 83 (1–5): 3–14. S2CID 40981759.
- Liu F, Ventura F, Doody J, Massagué J (1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Mol. Cell. Biol. 15 (7): 3479–86. PMID 7791754.
- Guan XY, Xu J, Anzick SL, Zhang H, Trent JM, Meltzer PS (1996). "Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer". Cancer Res. 56 (15): 3446–50. PMID 8758910.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. PMID 8889548.
- Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (1997). "cDNAs with long CAG trinucleotide repeats from human brain". Hum. Genet. 100 (1): 114–22. S2CID 25999127.
- Li H, Gomes PJ, Chen JD (1997). "RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8479–84. PMID 9238002.
- Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (1997). "AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer". Science. 277 (5328): 965–8. PMID 9252329.
- Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (1997). "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell. 90 (3): 569–80. S2CID 15284825.
- Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (1997). "TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1". J. Biol. Chem. 272 (44): 27629–34. PMID 9346901.
- Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG (1998). "Transcription factor-specific requirements for coactivators and their acetyltransferase functions". Science. 279 (5351): 703–7. PMID 9445475.
- Shirazi SK, Bober MA, Coetzee GA (1998). "Polymorphic exonic CAG microsatellites in the gene amplified in breast cancer (AIB1 gene)". Clin. Genet. 54 (1): 102–3. S2CID 1315265.
- Wang JC, Stafford JM, Granner DK (1998). "SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4". J. Biol. Chem. 273 (47): 30847–50. PMID 9812974.
- Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R (1999). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes Dev. 12 (22): 3488–98. PMID 9832502.
- Chen H, Lin RJ, Xie W, Wilpitz D, Evans RM (1999). "Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase". Cell. 98 (5): 675–86. S2CID 14697597.
- Ebisawa T, Tada K, Kitajima I, Tojo K, Sampath TK, Kawabata M, Miyazono K, Imamura T (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell Sci. 112 (20): 3519–27. PMID 10504300.
- Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM (2000). "Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2". Mol. Endocrinol. 13 (12): 2151–62. PMID 10598588.
- Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM (2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5. PMID 10655477.
- Leo C, Li H, Chen JD (2000). "Differential mechanisms of nuclear receptor regulation by receptor-associated coactivator 3". J. Biol. Chem. 275 (8): 5976–82. PMID 10681591.
- Font de Mora J, Brown M (2000). "AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor". Mol. Cell. Biol. 20 (14): 5041–7. PMID 10866661.
- Tan JA, Hall SH, Petrusz P, French FS (2000). "Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator". Endocrinology. 141 (9): 3440–50. PMID 10965917.
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