MAGEA11

Melanoma-associated antigen 11 is a protein that in humans is encoded by the MAGEA11 gene.[5][6] It is also involved in the androgen and progesterone receptor signaling pathways.

MAGEA11
Identifiers
Aliases	MAGEA11, CT1.11, MAGE-11, MAGE11, MAGEA-11, MAGE family member A11
External IDs	OMIM: 300344 MGI: 1333839 HomoloGene: 121637 GeneCards: MAGEA11
Gene location (Human) Chr. X chromosome (human)[1] Band Xq28 Start 149,688,228 bp[1] End 149,717,268 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A7.3|X 37.2 cM Start 72,222,017 bp[2] End 72,222,964 bp[2]
RNA expression pattern More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4110	17140
Ensembl	ENSG00000185247	ENSMUSG00000033343
UniProt	P43364	F2Z493
RefSeq (mRNA)	NM_001011544 NM_005366	NM_020280
RefSeq (protein)	NP_001011544 NP_005357	NP_064676
Location (UCSC)	Chr X: 149.69 – 149.72 Mb	Chr X: 72.22 – 72.22 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

MAGEA11 is an androgen coregulator specific to primates.[7] It was first identified in human melanomas, and has since been linked to several cancers.[8] It is observed on spermatogonia and primary spermatocytes, and in some prostate and breast cancers.[9]

This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as [dyskeratosis congenita]. Two transcript variants encoding different isoforms have been found for this gene.[6]

Interactions

MAGEA11 has been shown to interact with TCEA2,[10] androgen receptor[11][12] and SH2D4A.[10]

Genetics

MAGE-A genes have several noncoding exons followed by one protein-coding exon. MAGEA11 is mapped to the human chromosome X, forming a locus at q28 with other MAGE-A proteins. MAGE-A11 is located between two copies of MAGEA9 and MAGEA8, and is immediately downstream of the duplicated area. Its sublocus is about 2 Mb from the second sublocus containing the other MAGEA genes.[8]

Androgen receptor

MAGE-A11 is part of the androgen receptor signaling pathway in humans. It binds directly to the androgen receptor, promoting transcriptional through direct binding to the androgen receptor FXXLF motif region.[7][13] This control is specific to primates, and is due to a mutation in the androgen receptor from alanine to valine at residue 33, which extends the α-helix, which enables direct MAGE-A11 binding to the androgen receptor.[7] Post-translational modification of the protein by phosphorylation of Thr-360 and monoubiquitinylation of Lys-240 and Lys-245 also stabilizes the interaction with the androgen receptor.[14] MAGE-A11 likely links transcriptionally active androgen receptor dimers.[15] The MAGE-A11 dependent increase in androgen receptor transcriptional activity is mediated by a direct interaction of MAGE-A11 and transcriptional intermediary factor 2 (TIF2), suggesting that MAGE-A11 may act as a bridging factor to recruit other androgen receptor coactivators.[14] Mutations in the androgen receptor that interfere with binding of MAGE-A11 can cause partial androgen insensitivity syndrome.[16]

Progesterone receptor

MAGE-A11 also acts as an isoform-specific coregulator of full-length human progesterone receptor-B through an interaction with the receptor's N terminal.[15] It increases progesterone and glucocorticoid receptor activity, resulting in greater regulatory control over activation domain dominance compared to mice.[7]

Cancer

Most MAGE-A genes are not expressed in healthy tissues except testicular, ovarian, and placental germ cells. They are expressed in tumor cells. MAGE-A11 in particular shows high expression in a small number of tumors, but low levels in all others.[17]

Breast cancers

The MAGE-A family are linked to many kinds of cancerous tumors. MAGE-A11 expression is positively associated with HER-2 expression, and increased MAGE-A11 concentrations are associated with shorter life expectancies of patients with breast cancer.[18]

Prostate cancer

Increased expression of MAGE-A11 during prostate cancer progression enhances both the androgen receptor signaling pathway and cancer growth. MAGE-A11 mRNA levels increase significantly during androgen deprivation therapy to treat prostate cancer, and MAGE-A11 levels have been found to be highest in castration-recurrent prostate cancer.[15][19] The drastic increase is the result of DNA hypomethylation of a CpG island in the 5’ promoter of the MAGE-A11 gene. Cyclic AMP has also been found to increase MAGE-A11 expression as well as androgen receptor activity in prostate cancer cell lines, and extensive DNA methylation of the promoter inhibits the effects of cAMP.[19]

References

1. GRCh38: Ensembl release 89: ENSG00000185247 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000033343 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Rogner UC, Wilke K, Steck E, Korn B, Poustka A (Mar 1996). "The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28". Genomics. 29 (3): 725–31. doi:10.1006/geno.1995.9945. PMID 8575766.
6. "Entrez Gene: MAGEA11 melanoma antigen family A, 11".
7. Lui QS, Su S, Blackwelder AJ, Minges JT, Wilson EM (2011). "Gain in transcriptional activity by primate-specific coevolution of melanoma antigen-A11 and its interaction site in androgen receptor". Journal of Biological Chemistry. 286 (34): 29951–29963. doi:10.1074/jbc.m111.244715. PMC 3191036. PMID 21730049.
8. Artamonova II, Gelfand MS (2004). "Evolution of the exon-intron structure and alternative splicing of the MAGE-A family of cancer/testis antigens". Journal of Molecular Evolution. 59: 620–631. Bibcode:2004JMolE..59..620A. doi:10.1007/s00239-004-2654-3. PMID 15693618.
9. Sang M, Lian Y, Zhou X, Shan B (2011). "MAGE-A family: Attractive targets for cancer immunotherapy". Vaccine. 29 (47): 8496–8500. doi:10.1016/j.vaccine.2011.09.014. PMID 21933694.
10. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. England. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
11. Bai, Suxia; He Bin; Wilson Elizabeth M (Feb 2005). "Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction". Mol. Cell. Biol. United States. 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. ISSN 0270-7306. PMC 548016. PMID 15684378.
12. Bai, Suxia; Wilson Elizabeth M (Mar 2008). "Epidermal Growth Factor-Dependent Phosphorylation and Ubiquitinylation of MAGE-11 Regulates Its Interaction with the Androgen Receptor". Mol. Cell. Biol. United States. 28 (6): 1947–63. doi:10.1128/MCB.01672-07. PMC 2268407. PMID 18212060.
13. Askew EB, Bai S, Blackwelder AJ, Wilson EM (2010). "Transcriptional synergy between melanoma antigen gene protein-a11 (MAGE-A11) and p300 in androgen receptor signalling". Journal of Biological Chemistry. 285 (28): 21824–21836. doi:10.1074/jbc.m110.120600. PMC 2898404. PMID 20448036.
14. Askew EB, Bai S, Hnat AT, Minges JT, Wilson EM (2009). "Melanoma antigen gene protein-A11 (MAGE-11) F-box links the androgen receptor NH2-terminal transactivation domain to p160 coactivators". The Journal of Biological Chemistry. 284 (50): 34793–34808. doi:10.1074/jbc.m109.065979. PMC 2787342. PMID 19828458.
15. Minges JT, Su S, Grossman G, Blackwelder AJ, Pop EA, Mohler JL, Wilson EM (2013). "Melanoma Antigen-A11 (MAGE-A11) enhances transcriptional activity by linking androgen receptor dimers". Journal of Biological Chemistry. 288 (3): 1939–1952. doi:10.1074/jbc.m112.428409. PMC 3548502. PMID 23172223.
16. Lagarde WH, Blackwelder AJ, Minges JT, Hnat AT, Andrew T, French FS, Wilson EM (2012). "Androgen receptor exon 1 mutation causes androgen insensitivity by creating phosphorylation site and inhibiting melanoma antigen-A11 activation of NH2- and carboxyl-terminal interaction-debendent transactivation". Journal of Biological Chemistry. 287 (14): 10905–10915. doi:10.1074/jbc.m111.336081. PMC 3322816. PMID 22334658.
17. Serrano A, Lethe B, Melroisse J, Lurquin C, De Plaen E, Brasseur F, Rimoldi D, Boon T (1999). "Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries". International Journal of Cancer. 85 (5): 664–669. doi:10.1002/(sici)1097-0215(19991126)83:5<664::aid-ijc16>3.3.co;2-m.
18. Lian Y, Sang M, Ding C, Zhou X, Fan X, Xu Y, Lu W, Shan B (2012). "Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: A retrospective clinical study". Journal of Cancer Research and Clinical Oncology. 138 (3): 519–527. doi:10.1007/s00432-011-1122-x.
19. Karpf AR, Bai S, James SR, Mohler JL, Wilson EM (2009). "Increased expression of androgen receptor coregulator MAGE-11 in prostate cancer by DNA hypomethylation and cyclic AMP". Molecular Cancer Research. 7: 525–535. doi:10.1158/1541-7786.mcr-08-0400. PMC 2670465. PMID 19372581.

Further reading

• De Plaen E, Arden K, Traversari C, et al. (1994). "Structure, chromosomal localization, and expression of 12 genes of the MAGE family". Immunogenetics. 40 (5): 360–9. doi:10.1007/BF01246677. PMID 7927540.
• Jurk M, Kremmer E, Schwarz U, et al. (1998). "MAGE-11 protein is highly conserved in higher organisms and located predominantly in the nucleus". Int. J. Cancer. 75 (5): 762–6. doi:10.1002/(SICI)1097-0215(19980302)75:5<762::AID-IJC16>3.0.CO;2-8. PMID 9495246.
• Serrano A, Lethé B, Delroisse JM, et al. (1999). "Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries". Int. J. Cancer. 83 (5): 664–9. doi:10.1002/(SICI)1097-0215(19991126)83:5<664::AID-IJC16>3.0.CO;2-V. PMID 10521804.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Bai S, He B, Wilson EM (2005). "Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction". Mol. Cell. Biol. 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. PMC 548016. PMID 15684378.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.