Isolation and comparative expression analysis of the Myc‐regulatory proteins Mad1, Mad3, and Mnt during <i>Xenopus</i> development

Juergens, Kathrin; Rust, Barbara; Pieler, Tomas; Henningfeld, Kristine A.

doi:10.1002/dvdy.20470

Cited by 10 publications

(12 citation statements)

References 37 publications

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“…During Xenopus laevis development, the MNT orthologue XMnt is expressed in early embryos at the neurula stage and in migrating cranial neural crest cells [ 33 ]. The expression of Mnt in the neural tissues of mice and Xenopus seems consistent with the cleft palates and craniofacial deformities observed in Mnt -deficient mice [ 11 , 34 ].…”

Section: Mnt Expressionmentioning

confidence: 99%

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The Multiple Faces of MNT and Its Role as a MYC Modulator

Liaño-Pons

Arsenian-Henriksson

León

2021

Cancers

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MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

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Section: Mnt Expressionmentioning

confidence: 99%

“…The expression of Mnt in the neural tissues of mice and Xenopus seems consistent with the cleft palates and craniofacial deformities observed in Mnt -deficient mice [ 11 , 34 ]. In Xenopus , XMnt , XMad1, and XMad3 exhibit distinct areas of expression during embryogenesis, suggesting non-redundant functions [ 33 ].…”

Section: Mnt Expressionmentioning

confidence: 99%

The Multiple Faces of MNT and Its Role as a MYC Modulator

Liaño-Pons

Arsenian-Henriksson

León

2021

Cancers

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“…25 Within the adult mouse intestine, c-Myc is found to be expressed in dividing stem cells and Mad levels increase as cells differentiate and migrate up the crypt–villus axis. 26 Although Mad expression was localized in terminally differentiated cells during frog embryogenesis, 27 it remains uncertain if Mad has a similar role in differentiating the expanding adult epithelial stem cells into specialized cells as intestinal metamorphosis is completed in the frog.…”

mentioning

confidence: 99%

A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis

et al. 2017

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The Myc/Mad/Max network has long been shown to be an important factor in regulating cell proliferation, death and differentiation in diverse cell types. In general, Myc–Max heterodimers activate target gene expression to promote cell proliferation, although excess of c-Myc can also induce apoptosis. In contrast, Mad competes against Myc to form Mad–Max heterodimers that bind to the same target genes to repress their expression and promote differentiation. The role of the Myc/Mad/Max network during vertebrate development, especially, the so-called postembryonic development, a period around birth in mammals, is unclear. Using thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here that Mad1 is induced by T3 in the intestine during metamorphosis when larval epithelial cell death and adult epithelial stem cell development take place. More importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells during intestinal metamorphosis, suggesting that Mad1 may have a role in cell death during development. By using transcription activator-like effector nuclease-mediated gene-editing technology, we have generated Mad1 knockout Xenopus animals. This has revealed that Mad1 is not essential for embryogenesis or metamorphosis. On the other hand, consistent with its spatiotemporal expression profile, Mad1 knockout leads to reduced larval epithelial apoptosis but surprisingly also results in increased adult stem cell proliferation. These findings not only reveal a novel role of Mad1 in regulating developmental cell death but also suggest that a balance of Mad and Myc controls cell fate determination during adult organ development.

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“…d11.5 developing limb buds, Mxd3 is co-expressed with Mycn in proliferating mesenchyme adjacent to the epidermis whereas at d17.5, undifferentiated epiphyseal growth plate chondrocytes co-express Mxd3 and Myc. These differential expression patterns are maintained in species as diverse as Xenopus and are thus highly conserved throughout evolution [258].…”

Section: Mxd3mentioning

confidence: 99%

“…To better understand these relationships, we examined Myc, Mycn and Mxd1-4 transcripts in primary and recurrent low-grade gliomas (LGGs) cataloged in TCGA. We selected these tumors because of the distinct spatial and temporal expression of Mxd transcripts in the developing brain (see above) [27,31,258,262] and because Mxd3 is the only member of the Myc Network that correlates with unfavorable survival (Fig. 5).…”

Section: Mxd3mentioning

confidence: 99%

Normal and Neoplastic Growth Suppression by The Extended Myc Network

Wang¹,

Prochownik²

2022

Preprint

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Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1-4, Mnt and Mga) each of which heterodimerizes with Max and largely oppose Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted sets of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members with particular emphasis on the roles played by Max, Mlx and Mxd proteins in suppressing normal and neoplastic growth. These roles are complex due to the temporally- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.

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Isolation and comparative expression analysis of the Myc‐regulatory proteins Mad1, Mad3, and Mnt during Xenopus development

Cited by 10 publications

References 37 publications

The Multiple Faces of MNT and Its Role as a MYC Modulator

The Multiple Faces of MNT and Its Role as a MYC Modulator

A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis

Normal and Neoplastic Growth Suppression by The Extended Myc Network

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