Isolation and characterization of a MAGE gene family in the Xp21.3 region.

Muscatelli, Françoise; Walker, Ann P.; Plaen, Etienne De; Stafford, Amanda; Monaco, Anthony P.

doi:10.1073/pnas.92.11.4987

Cited by 91 publications

(47 citation statements)

References 23 publications

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“…Similarly, an FXXLF motif-dependent interaction was observed in the presence of DHT between GST-AR4-52 and 35 S-labeled AR624-919 containing the AR ligand binding domain. 35 S-labeled MAGE-11 migrates a 70 kDa, and 35 S-labeled AR ligand binding domain migrates a 41 kDa. We tested a previously described AR nuclear transport mutant, ARm4, that contains mutations in the AR bipartite nu- Immunoblots of GAL-AR peptides were performed using extracts from COS cells (2 ϫ 10 6 /10-cm dish) transfected with 10 g of GAL-AR peptide DNA with DEAEdextran.…”

Section: Resultsmentioning

confidence: 99%

“…However, a related MAGEB family of genes was recently reported that is ϳ60% homologous to the MAGE (MA-GEA) family (32). The MAGEB gene family maps to the Xp21 region of the X chromosome and is associated with a dosesensitive sex reversal phenotype (29,32,35) and with the DAX-1 gene, where mutations cause X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism (34).…”

Section: Vol 25 2005 Mage-11 Binds the Ar Fxxlf Motif 1249mentioning

confidence: 99%

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Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction

Bai

Wilson

2005

Molecular and Cellular Biology

126

160

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Gene activation by steroid hormone receptors involves the recruitment of the steroid receptor coactivator (SRC)/p160 coactivator LXXLL motifs to activation function 2 (AF2) in the ligand binding domain. For the androgen receptor (AR), AF2 also serves as the interaction site for the AR NH 2 -terminal FXXLF motif in the androgen-dependent NH 2 -terminal and carboxyl-terminal (N/C) interaction. The relative importance of the AR AF2 site has been unclear, since the AR FXXLF motif interferes with coactivator recruitment by competitive inhibition of LXXLL motif binding. In this report, we identified the X chromosome-linked melanoma antigen gene product MAGE-11 as an AR coregulator that specifically binds the AR NH 2 -terminal FXXLF motif. Binding of MAGE-11 to the AR FXXLF ␣-helical region stabilizes the ligand-free AR and, in the presence of an agonist, increases exposure of AF2 to the recruitment and activation by the SRC/p160 coactivators. Intracellular association between AR and MAGE-11 is supported by their coimmunoprecipitation and colocalization in the absence and presence of hormone and by competitive inhibition of the N/C interaction. AR transactivation increases in response to MAGE-11 and the SRC/p160 coactivators through mechanisms that include but are not limited to the AF2 site. MAGE-11 is expressed in androgen-dependent tissues and in prostate cancer cell lines. The results suggest MAGE-11 is a unique AR coregulator that increases AR activity by modulating the AR interdomain interaction.The androgen receptor (AR) is a member of the steroid receptor subfamily of nuclear receptors. Like other steroid receptors, AR has multiple domains involved in ligand and DNA binding and transcriptional activation. Recently, several unique properties of AR that distinguish it from other steroid receptors have gained attention. High-affinity androgen binding stabilizes AR (26), which is in contrast to most steroid receptors that are down regulated by agonist binding. Agonistinduced AR stabilization results in part from the NH 2 -terminal and carboxyl-terminal (N/C) interdomain interaction mediated by the androgen-dependent interaction between the AR NH 2 -terminal FXXLF motif and activation function 2 (AF2) in the ligand binding domain (16,17). The FXXLF motif 23 FQNLF 27 is part of an amphipathic ␣-helical region that is similar in structure to the LXXLL motifs of the steroid receptor coactivator (SRC)/p160 family of coactivators. The AR FXXLF motif is highly conserved among vertebrates, supporting its functional importance across species (13, 18). Recent cocrystal structures and binding studies have confirmed preferential binding of the FXXLF motif to the AR AF2 site and adaptability of AF2 to coactivator LXXLL motif binding through an induced-fit mechanism (15, 22). FXXLF motif binding to AF2 requires binding of ligands that display agonist activity in vivo (27). In transient transfection reporter gene assays, the N/C interaction is required for the activation of some, but not all, androgen-regulated genes (2, 18)...

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Section: Resultsmentioning

confidence: 99%

Section: Vol 25 2005 Mage-11 Binds the Ar Fxxlf Motif 1249mentioning

confidence: 99%

Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction

Bai

Wilson

2005

Molecular and Cellular Biology

126

160

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“…Since 1991, MAGE-1 (melanoma associated antigen) gene has been cloned from melanoma cells (van der Bruggen et al, 1991), there are up-to-date 17 MAGE genes being cloned (De Plaen et al, 1994;Lucas et al, 1998;Lurquin et al, 1997;Muscatelli et al, 1995;van der Bruggen et al, 1991). The MAGE genes are activated in spermatozoa but silent in normal somatic cells.…”

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confidence: 99%

Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells

Mou

Peng

et al. 2002

Br J Cancer

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The members of MAGE gene family are highly expressed in human hepatocellular carcinoma (HCC). In the present study, we tested the tumour-specific MAGE-1 and MAGE-3 transcripts in the peripheral blood of HCC patients by nested RT -PCR to detect the circulating tumour cells and evaluate their potential clinical implication. Of 30 HCC patients, the positive rate of MAGE-1 and MAGE-3 transcripts was 43.3% (13 out of 30) and 33.3% (10 out of 30) in PBMC samples, whilst the positive rate was 70% (21 out of 30) and 53.3% (16 out of 30) in the resected HCC tissue samples, respectively. The positivity for at least one MAGE gene transcript was 63.3% (19 out of 30) in PBMC samples of HCC patients and 83.3% (25 out of 30) in the resected HCC tissue samples. MAGE-1 and/or MAGE-3 mRNA were not detected in the PBMC of those patients from whom the resected HCC tissues were MAGE-1 or MAGE-3 mRNA negative, nor in the 25 PBMC samples from healthy donors. The detection of MAGE transcripts in PBMC was correlated with the advanced stages and tumour size of the HCC, being 82.4% (14 out of 17) in tumour stages III and IVa, 56.6% (five out of nine) in stage II, and null (nought out of four) in stage I. The serum a-FP in 33.3% (10 out of 30) of HCC patients was normal or slightly elevated (540 ng ml 71). However, six of these 10 patients (a-FP 540 ng ml 71 ) were MAGE-1 and /or MAGE-3 mRNA positive in their PBMC. The follow-up survey of MAGE mRNA in PBMC was performed in 12 patients. Seven patients with persistent MAGE-1 and/or MAGE-3 mRNA positive or from negative turned to positive died because of metastasis and/or recurrence. In striking contrast, all four patients with MAGE-1 and/or MAGE-3 mRNA from positive turned to negative and one patient with persistent MAGE-3 transcript negative are alive after last test. Collectively, detection of MAGE transcripts with follow-up survey in PBMC is a feasible and reliable assay for the early prediction of the relapse and prognosis of the HCC patients.

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“…This is due to the characterization of malignant tumors by melanoma, and due to the fact that low levels that are typically found in normal tissues, with the exception of the testicles and placenta (20). However, Jang et al discovered that MAGE mRNA was detected in corresponding normal tissues (21), and in 2006 Ito et al also revealed that MAGED4 expression was detected at low levels in normal tissues (19).…”

Section: Discussionmentioning

confidence: 99%

The significance of MAGED4 expression in non-small cell lung cancer as analyzed by real-time fluorescence quantitative PCR

Pang

Chen

et al. 2012

Oncology Letters

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Abstract. The aim of this study was to detect differences in the expression levels of melanoma-associated antigen D4 (MAGED4) mRNA between non-small cell lung cancer (NSCLC) tissues and normal tissues, and to compare differences in the expression levels of MAGED4 in tumor patients. Patients were grouped according to age, gender, smoking history, tumor size, pathological classification, degree of lung cancer cell differentiation and presence of lymph node metastasis. The expression levels of MAGED4 were detected using real-time fluorescence quantitative PCR. MAGED4 expression was higher in squamous cell carcinomas compared to adenocarcinomas (P<0.05), in poorly differentiated tissues compared to well-differentiated tissues (P<0.05), and in patients with lymph node metastasis compared to patients without lymph node metastasis (P<0.05). MAGED4 may be used as a specific antigen for NSCLC to influence the improvement of diagnosis, prognosis and immunological therapy outcomes in lung cancer patients.

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Isolation and characterization of a MAGE gene family in the Xp21.3 region.

Abstract: A human gene with strong homology to the

Cited by 91 publications

References 23 publications

Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction

Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction

Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells

The significance of MAGED4 expression in non-small cell lung cancer as analyzed by real-time fluorescence quantitative PCR

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