MYC

What Is MYC Protein?

MYC oncogene was originally discovered as the cellular homolog of v-myc, a retroviral oncogene from an avian myelocytomatosis virus. MYC, also called c-MYC, is a transcription factor that regulates the expression of genes controlling cell growth and proliferation. It is generally expressed in all dividing cells from embryonic and adult tissues.

What is the feature of the MYC structure?

MYC is made up of an N-terminal domain (NTD), a central region, and a C-terminal domain (CTD). Its NTD contains the transcriptional activation domain (TAD) and three "MYC boxes" 1-3, which are involved in transcription regulation and protein stability. The nuclear localization signal (NLS) lies in the central region and is associated with MYC cellular transforming activity, transcription, and apoptosis. The CTD holds the basic helix–loop–helix leucine zipper (bHLH-Zip) motif that is necessary for DNA-protein interactions.

The Functions of MYC Protein

MYC plays a central role in the transcriptional regulatory network that controls the expression of about 15% of human genes involved in cell cycle regulation, cell survival, protein synthesis, cell adhesion, and cytoskeleton, differentiation, and metabolism, signal transduction, transcription, translation, and MicroRNA synthesis. It is involved in the development of tumors and the induction of apoptosis.

The MYC signaling pathway

MYC exerts its diverse functions by ligating to its obligate partner MYC-associated factor X (MAX). MYC-MAX heterodimeric complexes recognize and bind to the "Enhancer box" (E-box) motifs (5′-CACGTG-3′) in the promoters of target genes to recruit multiple interacting proteins, thus leading to transcriptional activation. These genes are involved in cell growth and proliferation.

MYC and Cancer

In the majority of normal cells, MYC activation is inhibited through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence, thus blocking tumorigenesis. However, MYC is deregulated in numerous human cancers by chromosomal translocations and amplification, activation of upstream growth stimulatory signaling cascades, increased protein stability, and other different mechanisms. MYC overexpression has been found in numerous human tumors and is responsible for neoplastic transformation by deregulating central cellular processes including cell cycle progression, differentiation, metabolism, and angiogenesis.

Having a good understanding of MYC's expression and function can promote cancer treatment development. Bromodomain protein-mediated MYC's activation could be repressed by drug-like molecules, thus leading to tumor suppression in vivo. Targeting MYC-MAX dimerization or MYC-induced microRNA expression could also be a potent strategy to inhibit MYC on the path to cancer.