MAGEA11

Last updated
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
Orthologs
SpeciesHumanMouse
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: 71.27 – 71.27 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Nuclear receptor coactivator 2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

<span class="mw-page-title-main">FHL2</span> Protein-coding gene in the species Homo sapiens

Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the FHL2 gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.

<span class="mw-page-title-main">NCOA4</span> Protein-coding gene in the species Homo sapiens

Nuclear receptor coactivator 4, also known as Androgen Receptor Activator (ARA70), is a protein that in humans is encoded by the NCOA4 gene. It plays an important role in ferritinophagy, acting as a cargo receptor, binding to the ferritin heavy chain and latching on to ATG8 on the surface of the autophagosome.

<span class="mw-page-title-main">NKX3-1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Nkx-3.1, also known as NKX3-1, NKX3, BAPX2, NKX3A and NKX3.1 is a protein that in humans is encoded by the NKX3-1 gene located on chromosome 8p. NKX3-1 is a prostatic tumor suppressor gene.

<span class="mw-page-title-main">MAGEA1</span> Mammalian protein found in Homo sapiens

Melanoma-associated antigen 1 is a protein that in humans is encoded by the MAGEA1 gene.

<span class="mw-page-title-main">MAGEA3</span> Protein-coding gene in humans

Melanoma-associated antigen 3 (MAGE-A3) is a protein that in humans is encoded by the MAGEA3 gene.

<span class="mw-page-title-main">MAGED1</span> Protein-coding gene in the species Homo sapiens

Melanoma-associated antigen D1 is a protein that in humans is encoded by the MAGED1 gene.

<span class="mw-page-title-main">MAGEA4</span> Protein-coding gene in humans

Melanoma-associated antigen 4 is a protein that in humans is encoded by the MAGEA4 gene.

<span class="mw-page-title-main">UXT</span> Protein-coding gene in the species Homo sapiens

Protein UXT also known as androgen receptor trapped clone 27 (ART-27) protein is a protein that in humans is encoded by the UXT gene.

<span class="mw-page-title-main">RNF14</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the RNF14 gene.

<span class="mw-page-title-main">MAGEA2</span> Protein-coding gene in humans

Melanoma-associated antigen 2 is a protein that in humans is encoded by the MAGEA2 gene.

<span class="mw-page-title-main">MAGEB2</span> Protein-coding gene in humans

Melanoma-associated antigen B2 is a protein that in humans is encoded by the MAGEB2 gene.

<span class="mw-page-title-main">MAGEH1</span> Protein-coding gene in humans

Melanoma-associated antigen H1 is a protein that in humans is encoded by the MAGEH1 gene.

<span class="mw-page-title-main">MAGEA12</span> Protein-coding gene in humans

Melanoma-associated antigen 12 is a protein that in humans is encoded by the MAGEA12 gene.

<span class="mw-page-title-main">MAGEA9</span> Protein-coding gene in humans

Melanoma-associated antigen 9 is a protein that in humans is encoded by the MAGEA9 gene.

EPI-001 is the first inhibitor of the androgen receptor amino-terminal domain. The single stereoisomer of EPI-001, EPI-002, is a first-in-class drug that the USAN council assigned a new stem class "-aniten" and the generic name "ralaniten". This distinguishes the anitens novel molecular mechanism from anti androgens that bind the C-terminus ligand-binding domain and have the stem class "lutamide". EPI-001 and its stereoisomers and analogues were discovered by Marianne Sadar and Raymond Andersen, who co-founded the pharmaceutical company ESSA Pharma Inc for the clinical development of anitens for the treatment of castration-resistant prostate cancer (CRPC).

<span class="mw-page-title-main">Melanoma antigen family a, 8</span> Protein-coding gene in the species Homo sapiens

Melanoma antigen family A, 8 is a protein that in humans is encoded by the MAGEA8 gene.

Cancer/testis (CT) antigens are a group of proteins united by their importance in development and in cancer immunotherapy. In general, expression of these proteins is restricted to male germ cells in the adult animal. However, in cancer these developmental antigens are often re-expressed and can serve as a locus of immune activation. Thus, they are often classified as tumor antigens. The expression of CT antigens in various malignancies is heterogeneous and often correlates with tumor progression. CT antigens have been described in melanoma, liver cancer, lung cancer, bladder cancer, and pediatric tumors such as neuroblastoma. Gametogenesis offers an important role for many of these antigens in the differentiation, migration, and cell division of primordial germ cells, spermatogonia spermatocytes and spermatids. Because of their tumor-restricted expression and strong in vivo immunogenicity, CT antigens are identified as ideal targets for tumor specific immunotherapeutic approaches and prompted the development of several clinical trials of CT antigens-based vaccine therapy. CT antigens have been found to have at least 70 families so far, including about 140 members, most of which are expressed during spermatogenesis. Their expression are mainly regulated by epigenetic events, specifically, DNA methylation.

<span class="mw-page-title-main">MAGEA10</span> Protein-coding gene in humans

MAGEA10 is a protein-coding gene in humans clustered at chromosomal location Xq28.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185247 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "Entrez Gene: MAGEA11 melanoma antigen family A, 11".
  7. 1 2 3 4 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. 1 2 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 (5): 620–631. Bibcode:2004JMolE..59..620A. doi:10.1007/s00239-004-2654-3. PMID   15693618. S2CID   18690826.
  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. 1 2 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. S2CID   4427026.
  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. 1 2 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. 1 2 3 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. PMID   22198676. S2CID   23307117.
  19. 1 2 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 (4): 525–535. doi:10.1158/1541-7786.mcr-08-0400. PMC   2670465 . PMID   19372581.

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