Mitogen-activated protein kinase 1 (MAPK1), Tumor protein p53 (TP53), and MYC proto-oncogene (MYC) (MAPK1, TP53, and MYC)

This entry describes a grouping of three pivotal proteins in oncology: Mitogen-activated protein kinase 1 (MAPK1), Tumor protein p53 (TP53), and the MYC proto-oncogene (MYC). MAPK1, also known as ERK2, is a key kinase in the MAPK/ERK signaling pathway that translates extracellular growth signals into cellular responses such as proliferation and survival (UniProt P28482). TP53 is a critical tumor suppressor that maintains genomic integrity by inducing cell cycle arrest or apoptosis in response to cellular stress (UniProt P04637). MYC is a master transcription factor that regulates the expression of genes involved in cell growth, metabolism, and apoptosis, and is frequently deregulated in human cancers (UniProt P01106). These three proteins are functionally interconnected; for instance, MAPK1 can stabilize MYC protein levels, while p53 can repress MYC expression under stress conditions. Although they are high-value therapeutic targets, they present significant challenges, ranging from the "undruggable" nature of transcription factors like MYC and TP53 to the rapid emergence of resistance against MAPK1 inhibitors (PubMed PMID: 31068703).

Other names

Extracellular signal-regulated kinase 2ERK2P42MAPKTumor suppressor p53Antigen NY-CO-13c-MycProto-oncogene c-Myc

MAPK1 inhibitors block the ATP-binding site or allosteric sites to prevent phosphorylation of downstream targets; TP53-targeted therapies include MDM2 inhibitors that prevent p53 degradation and small molecules that refold mutant p53; MYC inhibitors primarily target the MYC/MAX dimerization interface to prevent DNA binding (PubMed PMID: 31068703).