publication . Article . 2015

MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4

Marcar, Lynnette; Ihrig, Bianca; Hourihan, John; Bray, Susan E; Quinlan, Philip R; Jordan, Lee B; Thompson, Alastair M; Hupp, Ted R; Meek, David W;
Open Access English
  • Published: 22 May 2015 Journal: PLoS ONE, volume 10, issue 5 (issn: 1932-6203, eissn: 1932-6203, Copyright policy)
  • Publisher: Public Library of Science
Abstract
<p>Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MA...
Subjects
mesheuropmc: endocrine systemneoplasms
free text keywords: Q, R, Research Article, Science, Medicine
54 references, page 1 of 4

1 van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643–1647. 1840703 [PubMed]

2 Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S (2001) An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res 61: 5544–5551. 11454705 [PubMed]

3 Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5: 615–625. 16034368 [PubMed]

4 Meek DW, Marcar L (2012) MAGE-A antigens as targets in tumour therapy. Cancer Lett 324: 126–132. doi: 10.1016/j.canlet.2012.05.011 22634429 [PubMed]

5 Sang M, Wang L, Ding C, Zhou X, Wang B, Lian Y, et al (2011) Melanoma-associated antigen genes—an update. Cancer Lett 302: 85–90. doi: 10.1016/j.canlet.2010.10.021 21093980 [PubMed]

6 Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188: 22–32. 12445278 [PubMed]

7 Liu W, Cheng S, Asa SL, Ezzat S (2008) The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res 68: 8104–8112. doi: 10.1158/0008-5472.CAN-08-2132 18829569 [PubMed]

8 Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, et al (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67: 9954–9962. 17942928 [PubMed]

9 Askew EB, Bai S, Blackwelder AJ, Wilson EM (2010) Transcriptional synergy between melanoma antigen gene protein-A11 (MAGE-11) and p300 in androgen receptor signaling. J Biol Chem 285: 21824–21836. doi: 10.1074/jbc.M110.120600 20448036 [OpenAIRE] [PubMed]

10 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 coact ivators. J Biol Chem 284: 34793–34808. doi: 10.1074/jbc.M109.065979 19828458 [OpenAIRE] [PubMed]

11 Laduron S, Deplus R, Zhou S, Kholmanskikh O, Godelaine D, De Smet C, et al (2004) MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription. Nucleic Acids Res 32: 4340–4350. 15316101 [OpenAIRE] [PubMed]

12 Marcar L, Maclaine NJ, Hupp TR, Meek DW (2010) Mage-A cancer/testis antigens inhibit p53 function by blocking its interaction with chromatin. Cancer Res 70: 10362–10370. doi: 10.1158/0008-5472.CAN-10-1341 21056992 [PubMed]

13 Monte M, Simonatto M, Peche LY, Bublik DR, Gobessi S, Pierotti MA, et al (2006) MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci U S A 103: 11160–11165. 16847267 [OpenAIRE] [PubMed]

14 Wilson EM (2010) Androgen receptor molecular biology and potential targets in prostate cancer. Ther Adv Urol 2: 105–117. doi: 10.1177/1756287210372380 21789088 [OpenAIRE] [PubMed]

15 Wong PP, Yeoh CC, Ahmad AS, Chelala C, Gillett C, Spiers V, et al (2014) Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer. Oncogene 33: 4579–4588. doi: 10.1038/onc.2014.45 24662835 [OpenAIRE] [PubMed]

54 references, page 1 of 4
Abstract
<p>Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MA...
Subjects
mesheuropmc: endocrine systemneoplasms
free text keywords: Q, R, Research Article, Science, Medicine
54 references, page 1 of 4

1 van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643–1647. 1840703 [PubMed]

2 Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S (2001) An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res 61: 5544–5551. 11454705 [PubMed]

3 Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5: 615–625. 16034368 [PubMed]

4 Meek DW, Marcar L (2012) MAGE-A antigens as targets in tumour therapy. Cancer Lett 324: 126–132. doi: 10.1016/j.canlet.2012.05.011 22634429 [PubMed]

5 Sang M, Wang L, Ding C, Zhou X, Wang B, Lian Y, et al (2011) Melanoma-associated antigen genes—an update. Cancer Lett 302: 85–90. doi: 10.1016/j.canlet.2010.10.021 21093980 [PubMed]

6 Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188: 22–32. 12445278 [PubMed]

7 Liu W, Cheng S, Asa SL, Ezzat S (2008) The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res 68: 8104–8112. doi: 10.1158/0008-5472.CAN-08-2132 18829569 [PubMed]

8 Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, et al (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67: 9954–9962. 17942928 [PubMed]

9 Askew EB, Bai S, Blackwelder AJ, Wilson EM (2010) Transcriptional synergy between melanoma antigen gene protein-A11 (MAGE-11) and p300 in androgen receptor signaling. J Biol Chem 285: 21824–21836. doi: 10.1074/jbc.M110.120600 20448036 [OpenAIRE] [PubMed]

10 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 coact ivators. J Biol Chem 284: 34793–34808. doi: 10.1074/jbc.M109.065979 19828458 [OpenAIRE] [PubMed]

11 Laduron S, Deplus R, Zhou S, Kholmanskikh O, Godelaine D, De Smet C, et al (2004) MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription. Nucleic Acids Res 32: 4340–4350. 15316101 [OpenAIRE] [PubMed]

12 Marcar L, Maclaine NJ, Hupp TR, Meek DW (2010) Mage-A cancer/testis antigens inhibit p53 function by blocking its interaction with chromatin. Cancer Res 70: 10362–10370. doi: 10.1158/0008-5472.CAN-10-1341 21056992 [PubMed]

13 Monte M, Simonatto M, Peche LY, Bublik DR, Gobessi S, Pierotti MA, et al (2006) MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents. Proc Natl Acad Sci U S A 103: 11160–11165. 16847267 [OpenAIRE] [PubMed]

14 Wilson EM (2010) Androgen receptor molecular biology and potential targets in prostate cancer. Ther Adv Urol 2: 105–117. doi: 10.1177/1756287210372380 21789088 [OpenAIRE] [PubMed]

15 Wong PP, Yeoh CC, Ahmad AS, Chelala C, Gillett C, Spiers V, et al (2014) Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer. Oncogene 33: 4579–4588. doi: 10.1038/onc.2014.45 24662835 [OpenAIRE] [PubMed]

54 references, page 1 of 4
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publication . Article . 2015

MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4

Marcar, Lynnette; Ihrig, Bianca; Hourihan, John; Bray, Susan E; Quinlan, Philip R; Jordan, Lee B; Thompson, Alastair M; Hupp, Ted R; Meek, David W;