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MYC family protein
The MYC-family of cellular proto-oncogenes encode three highly related nuclear phosphoprotein, C-MYC, N-MYC and L-MYC. The genes corresponding to these three proteins are located on chromosome 8, chromosome 2 and chromosome 1, respectively. The structure of MYC includes the first exon that does not encode a protein, and the other is the third exon that encodes a protein. The MYC gene belongs to an oncogene encoding a nuclear protein that encodes a nuclear DNA binding protein involved in cell cycle regulation. The MYC gene family and its products promote cell proliferation, immortalization, dedifferentiation and transformation.
C-MYC structure and function
Figure 2. The structure of C-MYC
The product of the C-MYC gene is the 62KD phosphorylated protein p62c-myc, which is located in the nucleus and is a nuclear protein consisting of 439 amino acids encoded by exons a and 3 of the c-myc gene. The C-MYC protein can be structurally divided into a transcriptional activation region, a non-specific DNA binding region, a nuclear target sequence, a basic region, a helix-loop-helix (HLH) and a leucine zipper region, among known transcription factors. It can mediate the oligomerization of proteins. The simultaneous presence of these two regions is unique to C-MYC protein. Among other proteins, it is rarely found. In C-MYC protein, the helix-ring-helix follows the alkaline the region reveals its interaction with DNA in a specific sequence. Studies in prokaryotes have shown that the basic region exists as a free loop and becomes a helix when bound to DNA in a special way. This region is the binding site of C-MYC protein to DNA specific sequence. The native protein C-MYC is a bHLHLZ (basic region/helix-loop-helix/leucine zipper) transcription factor that combines with a specific electronic box to form consistent core sequence 5'-CACGTG-3'.
In regulation cell growth and proliferation, the C-MYC protooncogene is depicted as a downsteam transduction pathway for receptor signaling that can cause positive or negative regulatory genes in C-MYC. The transcription factor C-MYC by C-MYC dimerizes with MAX and binds to the target DNA sequence or E-BOX (sequence 5'-CANNTG-3') to regulate transcriptional proliferation of genes involved in cell growth and apoptosis. The negative regulation of APC describes the WNT pathway b-catenin, which is involved in transactivation of C-MYC deletions during nuclear translocation such that loss of APC leads to constitutive carcinogenic C-MYC expression. When C-MYC is deregulated, acute sustained oncogenic C-MYC expression leads to activation of p53 or Arf checkpoints by gene amplification, loss of chromosomal translocations or upstream modulators (eg, APC). Moreover, the heterodimeric MYC-Max can also mediate transcription and gene suppression, and the heterodimeric MYC-Max interacts with key cofactors, such as transcription factor 2H (TFIIH) triggers transcriptional elongation or recruiting transcription/transcriptional domain correlation. Protein (TRRAP) GCN5, an acetylated histone that allows transcription of a target gene. MYC-Max also mediates gene suppression by regulating the transcription of target genes through the Miz-1 line together promoter (INR) element, which may be a silent C-MYC replacement nuclear phosphoprotein (NPM), a Miz-1 cofactor, or C-MYC induces the ribosomal protein RPL23, which retains the NPM nucleolus, away from Miz-1.C-MYC also regulates miRNA networks, and C-MYC regulates miRNA network by stimulating miR-17-92 to occlude and suppress dozens of miRs, including recent Let-7, which affects insulin signaling, miR-23a/b, and glutaminase Expression and miR-34a, which is shown to regulate lactate dehydrogenase (LDHA) expression. The miR-17 cluster contains miRNAs that target PTEN, thereby activating AKT, as well as those that target pro-apoptotic BimL or transcription factor E2F1. miRNAs downstream of C-MYC are also associated with EMT and angiogenesis.
C-MYC is one of the most frequently mutated genes in tumors. Since the overexpression of C-MYC is the cause of complete tumorigenesis, the interference with C-MYC expression is effective in tumor therapy, and C-MYC becomes a very attractive target for anticancer treatment. Deregulation of C-MYC has been found in most human tumors. In most cases, the rapid release of C-MYC is unregulated, but mutations in the C-MYC are rare. This enhanced or constitutive C-MYC expression can be the result of mutations in the C-MYC locus or in the signal transduction pathway that regulates C-MYC expression. Since C-MYC induces apoptosis in a normal cell without a sufficient amount of survival factor, activation of the oncogene C-MYC strongly selects a second mutation that abolishes the apoptotic pathway (eg, p53) or is used for activation. Two synergistic oncogenes. Inhibits apoptosis and stimulates cell survival (eg, Bcl-2, Bcl-xL, Ras). However, if C-MYC induces apoptosis inhibition (for example, by co-expression of the anti-apoptotic protein bcl-xl and bcl2, or due to an excess of local survival factors), C-MYC activation itself is sufficient to cause cells in no other conditions cancerous. Vice versa, activation of the oncogene C-MYC alone can induce persistent tumor regression, reverse and abolish tumorigenesis, and lead to complete permanent loss of tumor phenotype, a result that is a significant advance to the tumor treatment process. It also reminds us that C-MYC can be a key breakthrough point in cancer treatment.
Figure 1.C-MYC signaling pathway.
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