Myc

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Myc is a family of regulatory genes and proto-oncogenes that encode transcription factors. The Myc family consists of three related human genes: c-myc , l-myc , and n-myc . c-myc (sometimes also referred to as MYC ) is the first gene found in this family, due to homology with the viral gene v-myc .

In cancer, c-myc is often constitutively (continuously) expressed. This leads to increased expression of many genes, some of which are involved in cell proliferation, contributing to cancer formation. A general human translocation involving c-myc is essential for the development of most cases of Burkitt's lymphoma. Increased gene regulation Myc has also been observed in carcinoma of the cervix, colon, breast, lungs and abdomen. Myc is thus seen as a promising target for anti-cancer drugs.

In the human genome, C-myc is located on chromosome 8 and is believed to regulate the expression of 15% of all genes by binding to the order of the enhancer box (E-box).

In addition to its role as a classical transcription factor, N-myc can recruit histone acetyltransferases (HATs). It is possible to regulate the global chromatin structure through acetone acetylation.

Video Myc

Discovery

The Myc family was first established after the homology discovery between the oncogenes brought by Avian v irus, My elo c ytomatosis ( v-myc ) and the human genes are overexpressed in various c ancers ( c-Myc ). Then, the discovery of further homologous genes in humans causes the addition of n-Myc and l-Myc to the gene family.

The most frequently discussed example of c-Myc as oncogene is its implications in Burkitt's lymphoma. In Burkitt's lymphoma, cancer cells exhibit chromosomal translocation, most commonly between chromosome 8 and chromosome 14 [t (8, 14)]. This causes c-Myc to be placed downstream of the highly active immunoglobulin (Ig) promoter region, leading to overexpression of c-Myc .

Maps Myc

Structure

The protein product from the Myc family gene belongs to the Myc family of transcription factors, containing bHLH (helix-loop-helix base) and LZ (leucine zipper) structural motif. The bHLH motif, allowing the Myc protein to bind to DNA, while the zipper zipper TF zipper motif allows dimerization with Max, another bHLH transcription factor.

Myc mRNA contains IRES (internal ribosome entry site) that allows RNA to be translated into proteins when 5 'hatch-dependent translation is inhibited, such as during viral infection.

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Function

Myc protein is a transcription factor that activates the expression of many pro-proliferative genes by binding of the box-adder sequence (E-box) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding the transcription factor Miz-1 and replacing the p300 activator, it inhibits the expression of the Miz-1 target gene. In addition, myc has a direct role in controlling DNA replication.

Myc is activated on various mitogenic signals such as serum stimulation or by Wnt, Shh and EGF (via the MAPK/ERK pathway). By modifying the expression of the target gene, Myc activation produces many biological effects. The first to be discovered is its ability to induce cell proliferation (increase cyclometer regulation, decrease regulation of p21), but also play a very important role in regulating cell growth (increasing ribosomal and protein RNA regulation), apoptosis (lowering Bcl-2 regulation), differentiation, and cell stem cell renewal.

There are several studies that clearly show Myc's role in cell competition.

The main effect of c-myc is the proliferation of B cells.

c-Myc induces the expression of the MTDH gene (AEG-1) and in turn itself requires oncogenes AEG-1 for its expression.

src: clincancerres.aacrjournals.org

Myc-nick

Myc-nick is the cytoplasmic form of Myc produced by partial proteolytic cleavage of the lengths of c-Myc and N-Myc. Myc cleavage is mediated by the calpain family of calcium-dependent cytosolic proteases.

Myc cleavage by calpains is a constitutive process but is improved in conditions requiring rapid downregulation of the Myc level, such as during terminal differentiation. After cleavage, C-terminus Myc (containing DNA bindings domain) is degraded, while Myc-nick, the N-terminal 298-residue segment remains in the cytoplasm. Myc-nicks contain binding domains for histone acetyltransferases and for ubiquitin ligases.

The Myc-nick function is currently under investigation, but members of the new Myc family are found to regulate cell morphology, at least in part, by interacting with acetyl transferase to promote acetylation? -tubulin. Ectopic Expression Myc-nick accelerates myoblast differentiation into muscle cells.

src: cancerdiscovery.aacrjournals.org

Kepentingan klinis

Except for the initial response gene, Myc universally improves gene expression. Furthermore, the increase in regulation is not linear. The gene whose expression has risen significantly in the absence of Myc is firmly pushed in front of Myc, while the gene whose expression is low without Myc's presence gets little encouragement when Myc is present.

Inactivation of SUMO activating enzyme (SAE1/SAE2) in the presence of Myc hyperactivity results in mitotic calamities and cell death in cancer cells. Therefore SUMOylation inhibitors may be a possible treatment for cancer.

MYC gene amplification is found in a large number of epithelial ovarian cancer cases. In the TCGA dataset, Myc amplification occurs in some cancers, including breast, colorectal, pancreatic, gastric, and uterine cancers.

In the process of transforming experimental normal cells into cancer cells, the MYC gene can work in conjunction with the RAS gene.

The expression of Myc depends heavily on the function of BRD4 in some cancers. BET inhibitors have been used to successfully block the Myc function in pre-clinical cancer models and are currently being evaluated in clinical trials.

src: cancerdiscovery.aacrjournals.org

Animal model

During the discovery of the Myc gene, it was realized that reciprocal chromosomes translocated to chromosome 8 containing the immunoglobulin gene at resting point. Enhancers that normally induce the expression of immunoglobin genes now lead to overexpression of myc proto-oncogenes in lymphoma cells. To study the mechanism of tumorigenesis in Burkitt's lymphoma by mimicking the Myc expression pattern in this cancer cell, a transgenic mouse model was developed. The Myc gene that is placed under the weight gain chain control of IgM in transgenic mice causes particularly lymphoma. Then, to study the Myc effect on other types of cancer, transgenic mice that expose Myc in different tissues (liver, breast) are also made. In all of these mouse models the excessive expression of Myc causes tumorigenesis, describing the potential of Myc oncogenes. In a study with mice, reduced Myc expression was shown to induce longevity, with maximum median and maximum maximum time spans in both sexes and decreased mortality at all ages, better health, slower cancer progression, metabolism better and they have a smaller body.. Also, Less TOR, AKT, S6K and other changes in energy pathways and metabolism (such as AMPK, more oxygen consumption, more body movement, etc.). Research by John M. Sedivy and others using Cre-Loxp -recombinase to create one copy of Myc and this results in a "Haplo-insufficient" genotype recorded as Myc/-. The visible phenotype contradicts the effects of normal aging and is shared with many other long-lived mice models such as CR (caloric restriction) ames dwarf, rapamycin, metformin and resveratrol. One study found that the Myc and p53 genes were key to the survival of Chronic Myeloid Leukemia (CML) cells. Targeting Myc and p53 proteins with drugs gives positive results in mice with CML.

src: clincancerres.aacrjournals.org

Connection with Stem Cell

c-Myc plays a major role in the formation of pluripotent stem cells (iPSCs). This is one of the original factors found by Yamanaka et al to encourage the cell to return to a 'stem like' state along with transcription factors Oct4, Sox2 and Klf4). It has since been shown that it is possible to generate an iPSC without c-Myc .

src: www.bloodjournal.org

Interactions

Myc has been proven to interact with:

src: clincancerres.aacrjournals.org

See also

• Tag-Myc
• C-myc mRNA

src: mct.aacrjournals.org

References

src: jcs.biologists.org

Further reading

src: cancerdiscovery.aacrjournals.org

External links

• Myc Protein
• NCBI Myc Human Protein
• Myc's cancer gene
• myc Proto-Oncogene Proteins at US National Library of Medicine's Medical Subject Headings (MeSH)
• Produce iPS Cells from MEFS via Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4
• Drosophila Myc - The Interactive Fly
• FactorBook C-Myc

Source of the article : Wikipedia