MYC

Last updated
MYC
C-Myc-DNA complex.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MYC , MRTL, MYCC, bHLHe39, c-Myc, v-myc avian myelocytomatosis viral oncogene homolog, MYC proto-oncogene, bHLH transcription factor, Genes, myc, c-myc
External IDs OMIM: 190080; MGI: 97250; HomoloGene: 31092; GeneCards: MYC; OMA:MYC - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002467
NM_001354870

NM_001177352
NM_001177353
NM_001177354
NM_010849

RefSeq (protein)

NP_002458
NP_001341799

NP_001170823
NP_001170824
NP_001170825
NP_034979

Location (UCSC) Chr 8: 127.74 – 127.74 Mb Chr 15: 61.86 – 61.86 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

MYC proto-oncogene, bHLH transcription factor is a protein that in humans is encoded by the MYC gene [5] which is a member of the Myc family of transcription factors. The protein contains basic helix-loop-helix (bHLH) structural motif.

Contents

Function

This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017].

As a drug target

Under normal circumstances, c-Myc through its bHLHZip domain heterodimerizes with other transcription factors such as MAD, MAX, and MNT. Myc/Max dimers activate gene transcription, while Mad/Max and Mnt/Max dimers inhibit the activity of Myc. [6] c-MYC is over expressed in the majority of human cancers and in cancers where it is overexpressed, it drives proliferation of cancer cells. [7] [8]

A recombinant form of c-Myc called Omomyc in which four residues are mutated has been produced. [9] Omomyc heterodimers with c-Myc and inhibits c-Myc transcriptional activity. When the mouse cancer cell line NIH3T3 is treated with Omomyc, it inhibits proliferation. [9] In a mouse model of cancer in which cancer cells were genetically engineered to conditionally express Omomyc, Omomyc triggered tumor regression which was accompanied by reduced proliferation and increased apoptosis of the tumor tissue. [10]

The Omomyc displays high affinity for MAX (Myc-associated protein X) and for enhancer box element CACGTG DNA sequences, that result in the uncoupling of cellular proliferation from normal growth factor regulation and contribute to many of the phenotypic hallmarks of cancer. [11]

The recombinantly produced Omomyc miniprotein has been developed as a drug (OMO-103) and is currently in clinical trials. [12]

Related Research Articles

<span class="mw-page-title-main">Oncogene</span> Gene that has the potential to cause cancer

An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

<span class="mw-page-title-main">Burkitt lymphoma</span> Cancer of the lymphatic system

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc was the first gene to be discovered in this family, due to homology with the viral gene v-myc.

<span class="mw-page-title-main">N-Myc</span> Protein-coding gene in the species Homo sapiens

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.

<span class="mw-page-title-main">Transcription factor Jun</span> Mammalian protein found in Homo sapiens

Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun. The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.

<span class="mw-page-title-main">E2F1</span> Protein-coding gene in the species Homo sapiens

Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.

<span class="mw-page-title-main">REL</span> Protein-coding gene in the species Homo sapiens

The proto-oncogene c-Rel is a protein that in humans is encoded by the REL gene. The c-Rel protein is a member of the NF-κB family of transcription factors and contains a Rel homology domain (RHD) at its N-terminus and two C-terminal transactivation domains. c-Rel is a myeloid checkpoint protein that can be targeted for treating cancer. c-Rel has an important role in B-cell survival and proliferation. The REL gene is amplified or mutated in several human B-cell lymphomas, including diffuse large B-cell lymphoma and Hodgkin's lymphoma.

<span class="mw-page-title-main">BCL3</span> Protein-coding gene in the species Homo sapiens

B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.

<span class="mw-page-title-main">ID1</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein inhibitor ID-1 is a protein that in humans is encoded by the ID1 gene.

<span class="mw-page-title-main">PIM1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.

<span class="mw-page-title-main">MAX (gene)</span> Protein-coding gene in humans

MAX is a gene that in humans encodes the MAX transcription factor.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

<span class="mw-page-title-main">MXI1</span> Protein-coding gene in humans

MAX-interacting protein 1 is a protein that in humans is encoded by the MXI1 gene.

<span class="mw-page-title-main">MYCL</span> Protein-coding gene in the species Homo sapiens

L-myc-1 proto-oncogene protein is a protein that in humans is encoded by the MYCL1 gene.

<span class="mw-page-title-main">N-myc-interactor</span> Protein-coding gene in the species Homo sapiens

N-myc-interactor also known as N-myc and STAT interactor is a protein that in humans is encoded by the NMI gene.

<span class="mw-page-title-main">ID4</span> Protein-coding gene in humans

ID4 is a protein coding gene. In humans, it encodes the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.

<span class="mw-page-title-main">MNT (gene)</span> Protein-coding gene in the species Homo sapiens

MNT is a Max-binding protein that is encoded by the MNT gene

<span class="mw-page-title-main">PVT1</span> Non-coding RNA in the species Homo sapiens

Pvt1 oncogene, also known as PVT1 or Plasmacytoma Variant Translocation 1 is a long non-coding RNA gene. In mice, this gene was identified as a breakpoint site in chromosome 6;15 translocations. These translocations are associated with murine plasmacytomas. The equivalent translocation in humans is t(2;8), which is associated with a rare variant of Burkitt's lymphoma. In rats, this breakpoint was shown to be a common site of proviral integration in retrovirally induced T lymphomas. Transcription of PVT1 is regulated by Myc.

<span class="mw-page-title-main">GLIS1</span> Protein-coding gene

Glis1 is gene encoding a Krüppel-like protein of the same name whose locus is found on Chromosome 1p32.3. The gene is enriched in unfertilised eggs and embryos at the one cell stage and it can be used to promote direct reprogramming of somatic cells to induced pluripotent stem cells, also known as iPS cells. Glis1 is a highly promiscuous transcription factor, regulating the expression of numerous genes, either positively or negatively. In organisms, Glis1 does not appear to have any directly important functions. Mice whose Glis1 gene has been removed have no noticeable change to their phenotype.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136997 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022346 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "MYC MYC proto-oncogene, bHLH transcription factor [ Homo sapiens (human) ]" . Retrieved 2020-03-02.
  6. Dang CV, McGuire M, Buckmire M, Lee WM (February 1989). "Involvement of the 'leucine zipper' region in the oligomerization and transforming activity of human c-myc protein". Nature. 337 (6208): 664–6. Bibcode:1989Natur.337..664D. doi:10.1038/337664a0. PMID   2645525. S2CID   4326525.
  7. Madden SK, de Araujo AD, Gerhardt M, Fairlie DP, Mason JM (January 2021). "Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc". Molecular Cancer. 20 (1): 3. doi: 10.1186/s12943-020-01291-6 . PMC   7780693 . PMID   33397405.
  8. Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, Hansen AS, Gouw AM, Felsher DW (January 2022). "The MYC oncogene - the grand orchestrator of cancer growth and immune evasion". Nature Reviews. Clinical Oncology. 19 (1): 23–36. doi:10.1038/s41571-021-00549-2. PMC   9083341 . PMID   34508258.
  9. 1 2 Soucek L, Helmer-Citterich M, Sacco A, Jucker R, Cesareni G, Nasi S (November 1998). "Design and properties of a Myc derivative that efficiently homodimerizes". Oncogene. 17 (19): 2463–72. doi:10.1038/sj.onc.1202199. PMID   9824157. S2CID   22684888.
  10. Soucek L, Whitfield J, Martins CP, Finch AJ, Murphy DJ, Sodir NM, Karnezis AN, Swigart LB, Nasi S, Evan GI (October 2008). "Modelling Myc inhibition as a cancer therapy". Nature. 455 (7213): 679–83. Bibcode:2008Natur.455..679S. doi:10.1038/nature07260. PMC   4485609 . PMID   18716624. Creative Commons by small.svg  This article incorporates textfrom this source, which is available under the CC BY 4.0 license.
  11. Massó-Vallés D, Soucek L (April 2020). "Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc". Cells. 9 (4): 883. doi: 10.3390/cells9040883 . PMC   7226798 . PMID   32260326.
  12. "Results revealed from phase I clinical trial of the first drug to successfully inhibit the MYC gene, which drives many common cancers". European Organisation for. Research and Treatment of Cancer. 25 October 2022 via EurekAlert!.

Further reading


This article incorporates text from the United States National Library of Medicine, which is in the public domain.