Emerging roles of the MAGE protein family in stress response pathways

Gee, Rebecca R. Florke; Chen, Helen; Lee, Anna K.; Daly, Christina A; Wilander, Benjamin A.; Tacer, Klementina Fon; Potts, Patrick Ryan

doi:10.1074/jbc.rev120.008029

Cited by 54 publications

(60 citation statements)

References 394 publications

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“…However, MAGEL2 expression abrogated the increase of YTHDF2 in the nucleus after heat shock. These data suggest that MAGEL2 could regulate the translocation of YTHDF2 to the nucleus, by an as yet unknown mechanism ( 124 ).…”

Section: Discussionmentioning

confidence: 90%

The N-terminal domain of the Schaaf–Yang syndrome protein MAGEL2 likely has a role in RNA metabolism

Sanderson

Fahlman

Wevrick

2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionmentioning

confidence: 90%

The N-terminal domain of the Schaaf–Yang syndrome protein MAGEL2 likely has a role in RNA metabolism

Sanderson

Fahlman

Wevrick

2021

Journal of Biological Chemistry

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“…Melanoma antigens (MAGEs) not only drive tumorigenesis but also regulate pathways essential for diverse cellular and developmental processes. MAGEs are involved in molecular mechanisms in germ cell and neural development as well as oncogenic functions in cancer, and they have potential as therapeutic targets in disease [ 34 , 35 ].…”

Section: Immunotherapies Targeting Immunogenic Leukemia-associated An...mentioning

confidence: 99%

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Greiner

Götz

Wais

2022

IJMS

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Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.

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“…The human superfamily of MAGE proteins is divided into two groups based on their gene expression patterns and the functions of the encoded proteins, namely, type I-cancer/testis antigen MAGEs and type II-ubiquitous MAGEs. The type I MAGE proteins are further subdivided into the MAGE-A, -B, and -C families [16]. The MAGE-A family contains 15 members.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

Kim

et al. 2021

Cancers

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After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.

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Emerging roles of the MAGE protein family in stress response pathways

Cited by 54 publications

References 394 publications

The N-terminal domain of the Schaaf–Yang syndrome protein MAGEL2 likely has a role in RNA metabolism

The N-terminal domain of the Schaaf–Yang syndrome protein MAGEL2 likely has a role in RNA metabolism

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

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