MYC

What is MYC Protein?

MYC gene (MYC proto-oncogene, bHLH transcription factor) is a protein coding gene which situated on the long arm of chromosome 8 at locus 8q24. This gene is a proto-oncogene and encodes a nuclear phosphoprotein (also called c-Myc) 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. The MYC protein is consisted of 454 amino acids and MYC molecular weight is approximately 50.6 kDa.

What is the Function of MYC Protein?

MYC protein is a pluripotent transcription factor that plays a wide range of roles in cell proliferation, metabolism, angiogenesis, apoptosis, adhesion and differentiation. It plays a wide range of transcriptional regulatory roles by forming a heterodimer with MAX protein and directly binding to the E-box sequence on DNA (5'-CACGTG-3'). Under normal physiological conditions, the expression of c-Myc is strictly regulated, but when chromosomal translocation or signaling pathway gene mutation occurs, c-Myc will undergo expansion independent of growth factor stimulation, resulting in uncontrolled cell proliferation and tumor generation. Abnormal expression of c-Myc is present in approximately 70% of human tumors. In addition, MYC is involved in the regulation of metabolic diseases, including diabetes and fatty liver, and intestinal MYC has been identified as a new drug target for the treatment of metabolic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

MYC Related Signaling Pathway

c-Myc typically acts as a downstream target of the Ras-ERK signaling pathway, which plays a role in cell growth, differentiation, and tumorigenesis. Similar to the Ras-ERK signaling pathway, the PI3K-Akt signaling pathway also plays a key role in cell survival and proliferation, and c-Myc is an important effector. Wnt signaling negatively regulates β-catenin with APC, and the nuclear translocation of β-catenin can participate in trans activation of MYC, so APC deletion leads to constitutive carcinogenic MYC expression. c-Myc affects cell cycle progression and cell survival by regulating the expression of cell cycle related genes and inhibiting apoptosis proteins.

MYC Related Diseases

Abnormal expression and dysregulation of MYC protein play a key role in the development, progression, and treatment resistance of a variety of tumors, including but not limited to Burkitt lymphoma, multiple myeloma, colorectal cancer, breast cancer, lung cancer, and neuroblastoma. In these tumors, MYC gene amplification, overexpression or chromosomal translocation leads to the transcriptional regulation imbalance of its downstream genes, which promotes tumor cell proliferation, metabolic reprogramming, apoptosis inhibition and immune escape, making MYC a widely studied target in cancer therapy.

Fig1. c-MYC is responsible for the crosstalk between breast cancer cells and tumor microenvironment. (Fang-Yan Gao, 2023)

Bioapplications of MYC

MYC protein is a key transcription factor in the development of various tumors, and its central role in cell proliferation, metabolism and apoptosis makes it an important target for cancer therapy. Relevant applications include the development of small molecule inhibitors, peptides or protein drugs targeting MYC, and the use of MYC as a biomarker for early diagnosis and prognosis assessment of tumors. And to explore the role of MYC in the tumor microenvironment, to provide a new therapeutic idea for the personalized treatment of cancer and the combination of drug strategies.