MYC

For other uses, see MYC (disambiguation).

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.

MYC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A93, 1EE4, 1MV0, 1NKP, 2A93, 2OR9, 4Y7R
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
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q24.21 Start 127,735,434 bp[1] End 127,742,951 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 D1|15 26.19 cM Start 61,857,240 bp[2] End 61,862,223 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of thigh vena cava left uterine tube skin of abdomen gastric mucosa human penis mucosa of urinary bladder pericardium gallbladder cartilage tissue Top expressed in tail of embryo genital tubercle lumbar spinal ganglion lip Dermatocranium embryo yolk sac thymus endothelial cell of lymphatic vessel morula More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding protein dimerization activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding E-box binding protein binding protein-containing complex binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription repressor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleolus nucleus protein-containing complex Biological process Notch signaling pathway chromatin remodeling negative regulation of monocyte differentiation positive regulation of metanephric cap mesenchymal cell proliferation regulation of transcription, DNA-templated regulation of telomere maintenance positive regulation of epithelial cell proliferation positive regulation of fibroblast proliferation cellular response to UV oxygen transport negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II chromosome organization MAPK cascade cellular response to DNA damage stimulus positive regulation of cysteine-type endopeptidase activity involved in apoptotic process branching involved in ureteric bud morphogenesis negative regulation of cell division fibroblast apoptotic process positive regulation of mesenchymal cell proliferation positive regulation of response to DNA damage stimulus positive regulation of cell population proliferation positive regulation of DNA biosynthetic process regulation of gene expression canonical Wnt signaling pathway negative regulation of stress-activated MAPK cascade energy reserve metabolic process response to growth factor response to gamma radiation negative regulation of fibroblast proliferation positive regulation of transcription by RNA polymerase II cellular iron ion homeostasis beta-catenin-TCF complex assembly transcription, DNA-templated transcription by RNA polymerase II regulation of transcription by RNA polymerase II protein deubiquitination positive regulation of transcription, DNA-templated positive regulation of telomerase activity positive regulation of gene expression protein-DNA complex disassembly ERK1 and ERK2 cascade cellular response to hypoxia G1/S transition of mitotic cell cycle cytokine-mediated signaling pathway positive regulation of DNA methylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4609 17869 Ensembl ENSG00000136997 ENSMUSG00000022346 UniProt P01106 P01108 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

Function

For AUG and CUG, see Start codon.

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]

References

1. GRCh38: Ensembl release 89: ENSG00000136997 – Ensembl, May 2017
2. 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. 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. This article incorporates text from 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

• Hann SR, King MW, Bentley DL, Anderson CW, Eisenman RN (January 1988). "A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas". Cell. 52 (2): 185–95. doi:10.1016/0092-8674(88)90507-7. PMID 3277717. S2CID 3012009.
• Hiyama T, Haruma K, Kitadai Y, Ito M, Masuda H, Miyamoto M, Tanaka S, Yoshihara M, Sumii K, Shimamoto F, Chayama K (2001). "c-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma". Oncol. Rep. 8 (2): 289–92. doi:10.3892/or.8.2.289. PMID 11182042.
• Ruf IK, Rhyne PW, Yang H, Borza CM, Hutt-Fletcher LM, Cleveland JL, Sample JT (2001). "EBV Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt's Lymphoma". Epstein-Barr Virus and Human Cancer. Current Topics in Microbiology and Immunology. Vol. 258. pp. 153–60. doi:10.1007/978-3-642-56515-1_10. ISBN 978-3-642-62568-8. PMID 11443860. {{cite book}}: |journal= ignored (help)
• Hu HM, Arcinas M, Boxer LM (March 2002). "A Myc-associated zinc finger protein-related factor binding site is required for the deregulation of c-myc expression by the immunoglobulin heavy chain gene enhancers in Burkitt's lymphoma". J. Biol. Chem. 277 (12): 9819–24. doi:10.1074/jbc.M111426200. PMID 11777933.
• Hilker M, Tellmann G, Buerke M, Moersig W, Oelert H, Lehr HA, Hake U (2001). "Expression of the proto-oncogene c-myc in human stenotic aortocoronary bypass grafts". Pathol. Res. Pract. 197 (12): 811–6. doi:10.1078/0344-0338-00164. PMID 11795828.
• Feng XH, Liang YY, Liang M, Zhai W, Lin X (January 2002). "Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B)". Mol. Cell. 9 (1): 133–43. doi:10.1016/s1097-2765(01)00430-0. PMID 11804592.
• Kuschak TI, Kuschak BC, Taylor CL, Wright JA, Wiener F, Mai S (January 2002). "c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene". Oncogene. 21 (6): 909–20. doi:10.1038/sj.onc.1205145. PMID 11840336.
• Chettab K, Zibara K, Belaiba SR, McGregor JL (January 2002). "Acute hyperglycaemia induces changes in the transcription levels of 4 major genes in human endothelial cells: macroarrays-based expression analysis". Thromb. Haemost. 87 (1): 141–8. doi:10.1055/s-0037-1612957. PMID 11848444. S2CID 22124540.

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