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.
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].
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] Omomyc also can bind MYC monomers and prevent it entering the nucleus. [12]
The recombinantly produced Omomyc miniprotein has been developed as a drug (OMO-103) and is currently in clinical trials. [13]
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.
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).
Inhibitor of DNA-binding/differentiation proteins, also known as ID proteins comprise a family of proteins that heterodimerize with basic helix-loop-helix (bHLH) transcription factors to inhibit DNA binding of bHLH proteins. ID proteins also contain the HLH-dimerization domain but lack the basic DNA-binding domain and thus regulate bHLH transcription factors when they heterodimerize with bHLH proteins. The first helix-loop-helix proteins identified were named E-proteins because they bind to Ephrussi-box (E-box) sequences. In normal development, E proteins form dimers with other bHLH transcription factors, allowing transcription to occur. However, in cancerous phenotypes, ID proteins can regulate transcription by binding E proteins, so no dimers can be formed and transcription is inactive. E proteins are members of the class I bHLH family and form dimers with bHLH proteins from class II to regulate transcription. Four ID proteins exist in humans: ID1, ID2, ID3, and ID4. The ID homologue gene in Drosophila is called extramacrochaetae (EMC) and encodes a transcription factor of the helix-loop-helix family that lacks a DNA binding domain. EMC regulates cell proliferation, formation of organs like the midgut, and wing development. ID proteins could be potential targets for systemic cancer therapies without inhibiting the functioning of most normal cells because they are highly expressed in embryonic stem cells, but not in differentiated adult cells. Evidence suggests that ID proteins are overexpressed in many types of cancer. For example, ID1 is overexpressed in pancreatic, breast, and prostate cancers. ID2 is upregulated in neuroblastoma, Ewing’s sarcoma, and squamous cell carcinoma of the head and neck.
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.
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.
Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.
Bcl-6 is a protein that in humans is encoded by the BCL6 gene. BCL6 is a master transcription factor for regulation of T follicular helper cells proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation.
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.
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.
Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.
MAX is a gene that in humans encodes the MAX transcription factor.
MAX-interacting protein 1 is a protein that in humans is encoded by the MXI1 gene.
Transcription factor Maf also known as proto-oncogene c-Maf or V-maf musculoaponeurotic fibrosarcoma oncogene homolog is a transcription factor that in humans is encoded by the MAF gene.
L-myc-1 proto-oncogene protein is a protein that in humans is encoded by the MYCL1 gene.
N-myc-interactor also known as N-myc and STAT interactor is a protein that in humans is encoded by the NMI gene.
ID4 is a protein coding gene. In humans, it encodes for 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.
MNT is a Max-binding protein that is encoded by the MNT gene
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.
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.
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ignored (help)This article incorporates text from the United States National Library of Medicine, which is in the public domain.