Tumor protein p53 (TP53) and Mitogen-activated protein kinase 1 (MAPK1) (TP53 and MAPK1)

Tumor protein p53 (TP53) and Mitogen-activated protein kinase 1 (MAPK1) are two distinct proteins that play central, yet different, roles in cellular regulation and cancer progression. TP53 is a transcription factor known as the guardian of the genome, responsible for inducing cell cycle arrest, DNA repair, or apoptosis in response to cellular stress (Vogelstein et al., 2000). In contrast, MAPK1, also known as ERK2, is a protein kinase within the MAPK/ERK signaling pathway that promotes cell growth, survival, and differentiation in response to growth factors (Shaul & Seger, 2007). While both are significant therapeutic targets, they are not a single molecular complex; TP53 is frequently targeted to restore tumor suppression in p53-wildtype cancers, whereas MAPK1 is targeted to inhibit oncogenic signaling in MAPK-driven malignancies (Khoo et al., 2014). Mutations in TP53 are found in over half of all human cancers, making it a high-priority target for MDM2-p53 interaction inhibitors (Donehower et al., 2019). MAPK1 inhibition is often explored as a strategy to overcome resistance to upstream BRAF or MEK inhibitors in various solid tumors (Sullivan & Flaherty, 2013).

Other names

p53Antigen NY-CO-13Phosphoprotein p53Tumor suppressor p53BCC7LFS1TRP53ERK2Extracellular signal-regulated kinase 2MAP kinase 1MAPK 2p42-MAPKPRKM1PRKM2ERT1

TP53 is targeted by MDM2-p53 interaction inhibitors to prevent p53 degradation and restore its tumor-suppressive activity; MAPK1 is targeted by ERK inhibitors to block downstream proliferative signaling in the RAS-RAF-MEK-ERK pathway.