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'''Melanoma-associated antigen 11''' is a [[protein]] that in humans is encoded by the ''MAGEA11'' [[gene]].<ref name="pmid8575766">{{cite journal | author = Rogner UC, Wilke K, Steck E, Korn B, Poustka A | title = The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28 | journal = Genomics | volume = 29 | issue = 3 | pages = 725–31 |date=Mar 1996 | pmid = 8575766 | pmc = | doi = 10.1006/geno.1995.9945 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MAGEA11 melanoma antigen family A, 11| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4110| accessdate = }}</ref> It is also involved in the androgen and progesterone receptor signaling pathways.
'''Melanoma-associated antigen 11''' is a [[protein]] that in humans is encoded by the ''MAGEA11'' [[gene]].<ref name="pmid8575766">{{cite journal | author = Rogner UC, Wilke K, Steck E, Korn B, Poustka A | title = The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28 | journal = Genomics | volume = 29 | issue = 3 | pages = 725–31 |date=Mar 1996 | pmid = 8575766 | pmc = | doi = 10.1006/geno.1995.9945 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MAGEA11 melanoma antigen family A, 11| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4110| accessdate = }}</ref> It is also involved in the androgen and progesterone receptor signaling pathways.


MAGEA11 is an androgen coregulator specific to primates.<ref name="liu">{{cite journal | author = Lui QS, Su S, Blackwelder AJ, Minges JT, Wilson EM | title = Gain in transcriptional activity by primate-specific coevolution of melanoma antigen-A11 and its interaction site in androgen receptor | journal = Journal of Biological Chemistry | volume = 286 | issue = 34 | pages = 29951–29963 | year = 2011 }}</ref> It was first identified in human melanomas, and has since been linked to several cancers.<ref name="artamonova">{{cite journal | author = Artamonova II & Gelfand MS | title = Evolution of the exon-intron structure and alternative splicing of the MAGE-A family of cancer/testis antigens | journal = Journal of Molecular Evolution | volume = 59 | pages = 620–631 | year = 2004 }}</ref> It is observed on spermatogonia and primary spermatocytes, and in some prostate and breast cancers.<ref name="sang">{{cite journal | author = Sang M, Lian Y, Zhou X, Shan B | title = MAGE-A family: Attractive targets for cancer immunotherapy | journal = Vaccine | volume = 29 | issue = 47 | pages = 8496–8500 | year = 2011 }}</ref>
MAGEA11 is an androgen coregulator specific to primates.<ref name="liu">{{cite journal | author = Lui QS, Su S, Blackwelder AJ, Minges JT, Wilson EM | title = Gain in transcriptional activity by primate-specific coevolution of melanoma antigen-A11 and its interaction site in androgen receptor | journal = Journal of Biological Chemistry | volume = 286 | issue = 34 | pages = 29951–29963 | year = 2011 }}</ref> It was first identified in human melanomas, and has since been linked to several cancers.<ref name="artamonova">{{cite journal | author = Artamonova II & Gelfand MS | title = Evolution of the exon-intron structure and alternative splicing of the MAGE-A family of cancer/testis antigens | journal = Journal of Molecular Evolution | volume = 59 | pages = 620–631 | year = 2004 | doi=10.1007/s00239-004-2654-3}}</ref> It is observed on spermatogonia and primary spermatocytes, and in some prostate and breast cancers.<ref name="sang">{{cite journal | author = Sang M, Lian Y, Zhou X, Shan B | title = MAGE-A family: Attractive targets for cancer immunotherapy | journal = Vaccine | volume = 29 | issue = 47 | pages = 8496–8500 | year = 2011 | doi=10.1016/j.vaccine.2011.09.014}}</ref>


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==Androgen Receptor==
==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.<ref name=liu/><ref name="askew10">{{cite journal | author = Askew EB, Bai S, Blackwelder AJ & Wilson EM | title = Transcriptional synergy between melanoma antigen gene protein-a11 (MAGE-A11) and p300 in androgen receptor signalling. | journal = Journal of Biological Chemistry | volume = 285 | issue = 28 | pages = 21824–21836 | year = 2010 }}</ref> 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.<ref name=liu/> 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.<ref name="askew09">{{cite journal | author = Askew EB, Bai S, Hnat AT, Minges JT & Wilson EM | title = Melanoma antigen gene protein-A11 (MAGE-11) F-box links the androgen receptor NH2-terminal transactivation domain to p160 coactivators. | journal = The Journal of Biological Chemistry | volume = 284 | issue = 50 | pages = 34793–34808 | year = 2009 }}</ref> MAGE-A11 likely links transcriptionally active androgen receptor dimers.<ref name="minges">{{cite journal | author = Minges JT, Su S, Grossman G, Blackwelder AJ, Pop EA, Mohler JL & Wilson EM | title = Melanoma Antigen-A11 (MAGE-A11) enhances transcriptional activity by linking androgen receptor dimers | journal = Journal of Biological Chemistry| volume = 288 | issue = 3 | pages = 1939–1952 | year = 2013 }}</ref> 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.<ref name=askew09/> Mutations in the androgen receptor that interfere with binding of MAGE-A11 can cause partial androgen insensitivity syndrome.<ref name="lagarde">{{cite journal | author = Lagarde WH, Blackwelder AJ, Minges JT, Hnat AT, Andrew T, French FS, Wilson EM | title = 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 = Journal of Biological Chemistry | volume = 287 | issue = 14 | pages = 10905–10915 | year = 2012 }}</ref>
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.<ref name=liu/><ref name="askew10">{{cite journal | author = Askew EB, Bai S, Blackwelder AJ & Wilson EM | title = Transcriptional synergy between melanoma antigen gene protein-a11 (MAGE-A11) and p300 in androgen receptor signalling. | journal = Journal of Biological Chemistry | volume = 285 | issue = 28 | pages = 21824–21836 | year = 2010 | doi=10.1074/jbc.m110.120600}}</ref> 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.<ref name=liu/> 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.<ref name="askew09">{{cite journal | author = Askew EB, Bai S, Hnat AT, Minges JT & Wilson EM | title = Melanoma antigen gene protein-A11 (MAGE-11) F-box links the androgen receptor NH2-terminal transactivation domain to p160 coactivators. | journal = The Journal of Biological Chemistry | volume = 284 | issue = 50 | pages = 34793–34808 | year = 2009 | doi=10.1074/jbc.m109.065979}}</ref> MAGE-A11 likely links transcriptionally active androgen receptor dimers.<ref name="minges">{{cite journal | author = Minges JT, Su S, Grossman G, Blackwelder AJ, Pop EA, Mohler JL & Wilson EM | title = Melanoma Antigen-A11 (MAGE-A11) enhances transcriptional activity by linking androgen receptor dimers | journal = Journal of Biological Chemistry| volume = 288 | issue = 3 | pages = 1939–1952 | year = 2013 | doi=10.1074/jbc.m112.428409}}</ref> 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.<ref name=askew09/> Mutations in the androgen receptor that interfere with binding of MAGE-A11 can cause partial androgen insensitivity syndrome.<ref name="lagarde">{{cite journal | author = Lagarde WH, Blackwelder AJ, Minges JT, Hnat AT, Andrew T, French FS, Wilson EM | title = 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 = Journal of Biological Chemistry | volume = 287 | issue = 14 | pages = 10905–10915 | year = 2012 | doi=10.1074/jbc.m111.336081}}</ref>


==Progesterone Receptor==
==Progesterone Receptor==
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===Breast cancers===
===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.<ref name="lian">{{cite journal | author = Lian Y, Sang M, Ding C, Zhou X, Fan X, Xu Y, Lu W, Shan B | title = Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: A retrospective clinical study | journal = Journal of Cancer Research and Clinical Oncology | volume = 138 | issue = 3 | pages = 519–527 | year = 2012 }}</ref>
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.<ref name="lian">{{cite journal | author = Lian Y, Sang M, Ding C, Zhou X, Fan X, Xu Y, Lu W, Shan B | title = Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: A retrospective clinical study | journal = Journal of Cancer Research and Clinical Oncology | volume = 138 | issue = 3 | pages = 519–527 | year = 2012 | doi=10.1007/s00432-011-1122-x}}</ref>


===Prostate cancer===
===Prostate cancer===

Revision as of 20:24, 1 May 2014

Template:PBB Melanoma-associated antigen 11 is a protein that in humans is encoded by the MAGEA11 gene.[1][2] It is also involved in the androgen and progesterone receptor signaling pathways.

MAGEA11 is an androgen coregulator specific to primates.[3] It was first identified in human melanomas, and has since been linked to several cancers.[4] It is observed on spermatogonia and primary spermatocytes, and in some prostate and breast cancers.[5]

Template:PBB Summary

Interactions

MAGEA11 has been shown to interact with TCEA2,[6] Androgen receptor[7][8] and SH2D4A.[6]

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.[4]

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.[3][9] 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.[3] 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.[10] MAGE-A11 likely links transcriptionally active androgen receptor dimers.[11] 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.[10] Mutations in the androgen receptor that interfere with binding of MAGE-A11 can cause partial androgen insensitivity syndrome.[12]

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.[11] It increases progesterone and glucocorticoid receptor activity, resulting in greater regulatory control over activation domain dominance compared to mice.[3]

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.[13]

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.[14]

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.[11][15] 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.[15]

References

  1. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ "Entrez Gene: MAGEA11 melanoma antigen family A, 11".
  3. ^ a b c d 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b 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. doi:10.1007/s00239-004-2654-3.
  5. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b Rual, Jean-François (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062). England: 1173–8. doi:10.1038/nature04209. PMID 16189514. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Bai, Suxia (Feb 2005). "Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction". Mol. Cell. Biol. 25 (4). United States: 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. ISSN 0270-7306. PMC 548016. PMID 15684378. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  8. ^ Bai, Suxia (Mar 2008). "Epidermal Growth Factor-Dependent Phosphorylation and Ubiquitinylation of MAGE-11 Regulates Its Interaction with the Androgen Receptor". Mol. Cell. Biol. 28 (6). United States: 1947–63. doi:10.1128/MCB.01672-07. PMC 2268407. PMID 18212060. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  9. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  10. ^ a b 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  11. ^ a b c 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  12. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  13. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ a b 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading

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