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Cells
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Regulation and Function of the Myc Oncogene
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Regulation and Function of the Myc Oncogene

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 34586

Special Issue Information

Dear Colleagues,

The MYC proto-oncoproteins, c-MYC, MYCN and MYCL, are structurally and functionally conserved transcription factors of the basic helix–loop–helix leucine zipper (bHLHZip) family. They are part of a complex transcriptional network involving other members of the bHLHZip family, including MAX and the MXD proteins. We have studied these proteins for more than 40 years, but still, there is much to learn. MYC proteins play fundamental roles in cell biology during development and cell division, including the regulation of metabolism, protein synthesis, cell adhesion, senescence, and apoptosis. In addition to specific gene regulation through the activation or repression of target genes, MYC is involved in general transcriptional amplification of already active promoters, leading to primary or secondary mRNA amplification. Furthermore, MYC proteins can mediate transcriptional-independent processes, such as DNA replication or mRNA cap methylation. Importantly, MYC genes are overexpressed, by means of translocation, amplification, increased translation or protein stability, in a wide range of human cancers and are frequently associated to aggressiveness and poor outcome. Several approaches to interfere with MYC activity have been explored, with so far limited applicability in the clinical setting. In this Special Issue of Cells, we aim to collect the current knowledge on this fascinating family of proteins, during health and disease in mammals as well as in other organisms. This includes all aspects of MYC biology, such as gene expression, protein stability and regulation, the manifold effects in cellular processes, and physiological control of stemness and tissue development. There will be a special focus on the pathological effects of MYC deregulation and the opportunities for therapeutic intervention in human disease, mainly cancer but also other MYC-associated syndromes.

We are looking forward to your contribution shedding light on this important and enigmatic protein and hope that together, we will bring the field forward!
Best regards,

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • MYC transcriptional network
  • Development, cell cycle, and apoptosis
  • Stemness
  • Cancer
  • Inhibition of MYC

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Published Papers (4 papers)

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Review

27 pages, 2386 KiB  
Review
Structural and Biophysical Insights into the Function of the Intrinsically Disordered Myc Oncoprotein
by Marie-Eve Beaulieu, Francisco Castillo and Laura Soucek
Cells 2020, 9(4), 1038; https://doi.org/10.3390/cells9041038 - 22 Apr 2020
Cited by 64 | Viewed by 7160
Abstract
Myc is a transcription factor driving growth and proliferation of cells and involved in the majority of human tumors. Despite a huge body of literature on this critical oncogene, our understanding of the exact molecular determinants and mechanisms that underlie its function is [...] Read more.
Myc is a transcription factor driving growth and proliferation of cells and involved in the majority of human tumors. Despite a huge body of literature on this critical oncogene, our understanding of the exact molecular determinants and mechanisms that underlie its function is still surprisingly limited. Indubitably though, its crucial and non-redundant role in cancer biology makes it an attractive target. However, achieving successful clinical Myc inhibition has proven challenging so far, as this nuclear protein is an intrinsically disordered polypeptide devoid of any classical ligand binding pockets. Indeed, Myc only adopts a (partially) folded structure in some contexts and upon interacting with some protein partners, for instance when dimerizing with MAX to bind DNA. Here, we review the cumulative knowledge on Myc structure and biophysics and discuss the implications for its biological function and the development of improved Myc inhibitors. We focus this biophysical walkthrough mainly on the basic region helix–loop–helix leucine zipper motif (bHLHLZ), as it has been the principal target for inhibitory approaches so far. Full article
(This article belongs to the Special Issue Regulation and Function of the Myc Oncogene)
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19 pages, 1362 KiB  
Review
Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc
by Daniel Massó-Vallés and Laura Soucek
Cells 2020, 9(4), 883; https://doi.org/10.3390/cells9040883 - 4 Apr 2020
Cited by 94 | Viewed by 9771
Abstract
First designed and published in 1998 as a laboratory tool to study Myc perturbation, Omomyc has come a long way in the past 22 years. This dominant negative has contributed to our understanding of Myc biology when expressed, first, in normal and cancer [...] Read more.
First designed and published in 1998 as a laboratory tool to study Myc perturbation, Omomyc has come a long way in the past 22 years. This dominant negative has contributed to our understanding of Myc biology when expressed, first, in normal and cancer cells, and later in genetically-engineered mice, and has shown remarkable anti-cancer properties in a wide range of tumor types. The recently described therapeutic effect of purified Omomyc mini-protein—following the surprising discovery of its cell-penetrating capacity—constitutes a paradigm shift. Now, much more than a proof of concept, the most characterized Myc inhibitor to date is advancing in its drug development pipeline, pushing Myc inhibition into the clinic. Full article
(This article belongs to the Special Issue Regulation and Function of the Myc Oncogene)
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16 pages, 1046 KiB  
Review
The Role of MYC and PP2A in the Initiation and Progression of Myeloid Leukemias
by Raffaella Pippa and Maria D. Odero
Cells 2020, 9(3), 544; https://doi.org/10.3390/cells9030544 - 26 Feb 2020
Cited by 22 | Viewed by 5617
Abstract
The MYC transcription factor is one of the best characterized PP2A substrates. Deregulation of the MYC oncogene, along with inactivation of PP2A, are two frequent events in cancer. Both proteins are essential regulators of cell proliferation, apoptosis, and differentiation, and they, directly and [...] Read more.
The MYC transcription factor is one of the best characterized PP2A substrates. Deregulation of the MYC oncogene, along with inactivation of PP2A, are two frequent events in cancer. Both proteins are essential regulators of cell proliferation, apoptosis, and differentiation, and they, directly and indirectly, regulate each other’s activity. Studies in cancer suggest that targeting the MYC/PP2A network is an achievable strategy for the clinic. Here, we focus on and discuss the role of MYC and PP2A in myeloid leukemias. Full article
(This article belongs to the Special Issue Regulation and Function of the Myc Oncogene)
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24 pages, 1105 KiB  
Review
MYC’s Fine Line Between B Cell Development and Malignancy
by Oriol de Barrios, Ainara Meler and Maribel Parra
Cells 2020, 9(2), 523; https://doi.org/10.3390/cells9020523 - 24 Feb 2020
Cited by 22 | Viewed by 11111
Abstract
The transcription factor MYC is transiently expressed during B lymphocyte development, and its correct modulation is essential in defined developmental transitions. Although temporary downregulation of MYC is essential at specific points, basal levels of expression are maintained, and its protein levels are not [...] Read more.
The transcription factor MYC is transiently expressed during B lymphocyte development, and its correct modulation is essential in defined developmental transitions. Although temporary downregulation of MYC is essential at specific points, basal levels of expression are maintained, and its protein levels are not completely silenced until the B cell becomes fully differentiated into a plasma cell or a memory B cell. MYC has been described as a proto-oncogene that is closely involved in many cancers, including leukemia and lymphoma. Aberrant expression of MYC protein in these hematological malignancies results in an uncontrolled rate of proliferation and, thereby, a blockade of the differentiation process. MYC is not activated by mutations in the coding sequence, and, as reviewed here, its overexpression in leukemia and lymphoma is mainly caused by gene amplification, chromosomal translocations, and aberrant regulation of its transcription. This review provides a thorough overview of the role of MYC in the developmental steps of B cells, and of how it performs its essential function in an oncogenic context, highlighting the importance of appropriate MYC regulation circuitry. Full article
(This article belongs to the Special Issue Regulation and Function of the Myc Oncogene)
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