CMYC is composed of three exons spanning over 4 kb with the second and third exons encoding most MYC protein. These two exons have at least 70% sequence homology among species. However, exon1 is untranslated whose sequence is not as well conserved through evolution. The exon1 has been postulated to play a role in translational control and mRNA stability. There are four MYC transcriptional promoters. In normal cells, promoter P2 contributes to approximately 75% of total MYC transcripts while P1 accounts for most the remaining 25% transcripts (Dang CV 2012).

MYC mRNA contains an IRES (internal ribosome entry site) that allows the RNA to be translated into protein when 5 cap-dependent translation is inhibited, such as during viral infection.

439 amino acids and 48 kDa in the p64; 454 amino acids in the p67 (15 additional amino acids in N-term; contains from N-term to C-term: a transactivation domain, an acidic domain, a nuclear localization signal, a basic domain, an helix-loop-helix motif, and a leucin zipper; DNA binding protein.

Expressed in almost all proliferating cells in embryonic and adult tissues; in adult tissues, expression correlates with cell proliferation; abnormally high expression is found in a wide variety of human cancers.

located predominantly in the nucleus.
The myc protein contains an unstructured N-terminal transcriptional regulatory domain followed by a nuclear localization signal and a C-terminal region with a basic DNA-binding domain tied to a helix-loop-helix-leucine zipper (bHLHZip) dimerization motif. The bHLHzip motif of MYC dimerizes with the MAX, which is a prerequisite for specific binding to DNA at E-box sequences (5-CA(C/T)G(T/C)G-3) (Dang 2012). Upon DNA binding the MYC/MAX heterodimer recruits co-factors, which mediate multiple effects of MYC on gene expression in a context-dependent manner. This dimerization process is essential for induction of cell cycle progression, apoptosis, and transformation suggesting that MYC exerts its oncogenic effects by transactivation of target genes via E-boxes (Amati B, Land H, 1994; Grandori C et al 2000). The coding exons of MYC encode for the N-terminal region which has a transcriptional regulatory domain, a region that contains conserved MYC Boxes I and II, followed by MYC Box III and IV, and a nuclear targeting sequence. The N-terminal region will bind with co-activator complexes, making MYC acts as the transcription or repression factor (Cowling et al 2006).
In normal cells, MYC is tightly regulated by mitotic and developmental signals, and in turn, it regulates the expression of downstream target genes. Both MYC mRNA and protein have very short half-lives in normal cells (20-30 minutes each). Without appropriate positive regulatory signals, MYC protein levels are low and insufficient to promote cellular proliferation. In addition, MYC protein is rapidly degraded by the ubiquitin-linked proteasome machinery. The short-life and instability of MYC protein and mRNA together would seem to be an effective safeguard mechanism of MYC regulation (Herrick and Ross et al, 1994). However, these controls are lost in cancer cells, resulting in aberrantly high levels of MYC protein. In its physiological role, MYC is broadly expressed during embryogenesis and in tissue with high proliferative capacity such as skin epidermis and gut. Its expression strongly correlates with cell proliferation.

MYC functions as a transcriptional regulator, capable to induce or repress the expression of a large number of genes, which are thought to mediate its biological functions (Adhikary and Eilers 2005). MYC protein cannot form homodimers, but it binds to MAX that is an obligate heterodimeric partner for MYC in mediating its functions. The MYC-MAX complex is a potent activator of transcription for a critical set of cellular target genes. Initially, two additional partners for Max had been identified, MXI1 and MXD1 (Mad1). Two more Max-interacting proteins, MXD3 (Mad3) and MXD4 (Mad4), which behave similarly to MXD1 have been reported. The transcription activation is mediated exclusively by MYC-MAX complexes, whereas MAX-MXD1 and MAX-MXI1 complexes mediate transcription repression through identical binding sites. Max expression is not highly regulated and its protein is very stable; in contrast, MXD1 protein appears to have a short half-life and to be highly regulated (Amati and Land, 1994). MXI1 protein is also regulated. MYC-MAX heterodimers activate transcription through interactions with transcriptional coactivators ( TRRAP, ACTL6A (BAF53)) and their associated histone acetyltransferases and/or ATPase/helicases, resulting in transition from the G0/1 phase to the S phase (Nilsson and Cleveland, 2003). Several studies have established that MAX is essential for MYC-mediated gene transactivation, transformation, cell cycle progression and apoptosis. On the other hand, overexpression of MXI1 and MXD1 can antagonize MYC activity in cellular transformation assays and proliferation and can diminish the malignant phenotype of tumor cells. MXD1 can also inhibit apoptosis and reverse the differentiation blocking effect of MYC in leukemia cells. (Dang 2012). These findings are consistent with the concept that MXD1 and MXI1 suppress MYC function. In addition to interacting with proteins involved in transcription regulation, MYC also interacts with enzymes controlling histone methylation.
Target Genes Thousands of MYC target genes have been identified by following mRNA levels in experimentally controlled activation of the MYC gene (Menssen and Hermeking 2002). In general, genes targeted by MYC include mediators of metabolism, biosynthesis, and cell cycle progression, such that aberrant MYC expression is associated with uncontrolled cell growth, division, and metastasis, whereas loss or inhibition of MYC expression hinders growth, promotes differentiation, and sensitizes cells to DNA damage (Miller 2012; Hsieh 2015). Different target genes are regulated under specific conditions for specific cell types. Some of the most biologically important targets are CCND2 (cyclin D2), and cyclin-dependent kinases (CDKs), resulting in accelerated cell cycling; down-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) with consequent up-regulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/ MTOR) pathway; and stabilization of the proapoptotic protein and tumor suppressor TP53, (Hoffman and Liebermann 2008; Dang 2012) which can bypass the apoptotic BCL2 program. MYC, on the other hand, activates many ribosomal protein genes including RPL23, which binds to and retains NPM1 in the nucleolus, thereby inhibiting PIAS2 (Miz-1) activity (Wanzel, 2008). MYC itself is modulated by NPM1, which acts as a positive MYC coactivator (Schneider A 1997; Grandori C et al., 2005; Li Z, et al 2008).
MYC-targeted gene network also contains non-protein coding targets; among those are microRNAs (miRNAs). The miRNAs are 18- 22 nucleotides non-coding RNAs that negatively regulate gene expression at the post-transcriptional level via binding to 3-UTRs of target mRNAs and mediate translational repression or mRNA degradation. Some miRNA function as an oncogene while others behave as tumor suppressor gene, in a cell-typed manner. Growing evidences have suggested that MYC regulates the expression of a number of miRNAs, resulting in widespread repression of miRNA and, at the same time, MYC being subjected to regulation by miRNAs, leading to sustained MYC activity and the corresponding MYC downstream pathways (Chang et al, 2008). Thus, these combined effects of MYC overexpression and downregulation of miRNAs play a central regulatory role in the MYC oncogenic pathways. For example, MYC upregulates expression of miR-17-92 clusters a set of oncogenic miRNAs, which contains six mature miRNAs. Recently, miR-19 was identified as the key oncogenic component of this cluster (Tao et al 2014; Koh 2016). Overexpression of miR-17-92 is observed in a large fraction of human cancers, including carcinomas of the breast, lung, and colon; medulloblastomas; neuroblastomas and B-cell lymphoma. The miR17-92 is commonly amplified at 13q31 in several subtypes of aggressive lymphomas. Its oncogenic function is reflected by down-regulation of PTEN, TP53 and E2F1, causing the activation of the PI3K/AKT pathway and inhibiting cellular apoptosis. The functional interaction between miR-17`92 and MYC is further emphasized by the finding that MYC is a potent transcriptional activator of miR-17-92 (ODonnell et al. 2005), thus suggesting that miR-17-92 may contribute to the oncogenic properties of MYC. Another MYC-induced miRNA, MIR22, was recently shown to act as a potent proto-oncogenic miRNA by genome-wide deregulation of the epigenetic state through inhibition of methylcytosine dioxygenase TET proteins. In addition, MIR22 was characterized as a key regulator of self-renewal in the hematopoietic system. MYC also represses several miRNAs with tumor suppressor function such as MIR15A/ MIR16-1 and miR-34 that regulate apoptosis by targeting BCL2 and TP53 respectively. Likewise MYC is negatively regulated by several miRNAs such as miR-34 and MIR494. The auto functional interaction between MYC and miRNAs target genes maintains persistent expression of MYC, thus promoting the malignant phenotype (Tao et al 2014; Jackstadt 2015).
Furthermore, over expression of MYC can induce apoptosis. The apoptosis triggered or sensitized by MYC can be either TP53-dependent or TP53 independent, determined by the cell type and apoptotic trigger. The mechanisms of MYC-mediated apoptosis may involve several pathways. Overexpression of MYC increases DNA replication and possibly results in DNA damage that, in turn, triggers a TP53-mediated response leading to apoptosis, in some cell types (Hoffman and Libermann, 2008). As well, MYC expression seems to downregulate antiapoptotic proteins such as BCL2 or BCL2L1 (Bcl-XL) and upregulate pro-apoptotic elements such as BCL2L11 (BIM).
MYC also plays an important role in mitochondrial biogenesis. Large scale studies of gene expression in rat and human systems first suggested that MYC overexpression can induce nuclear encoded mitochondrial genes. In addition, MYC has been shown to bind to the promoters of genes encoding proteins involved in mitochondrial function. Using an inducible MYC-dependent human B cell model of cell proliferation it was shown that mitochondrial biogenesis is completely dependent on MYC expression. Moreover, the genes involved with mitochondrial biogenesis are among the MYC target genes most highly induced (Gao et al 2009).