What is the p53 Pathway?

The p53 pathway is a complex network of proteins and pathways that act in a coordinated fashion to regulate cell growth, death, and differentiation. The p53 pathway is also known as the tumor suppressor pathway because it is critical in controlling cell growth and maintaining genetic stability.

However, in most human cancers, the TP53 gene is mutated, leading to inactivation of the p53 protein. The p53 protein is a transcription factor encoded by the TP53 gene that acts as a tumor suppressor. In normal cells, p53 is activated in response to various stress signals like DNA damage, oncogene activation, and replication stress.

Mechanism of Action

Activated p53 promotes the transcription of genes involved in cell cycle arrest, DNA repair, senescence, and apoptosis, thereby preventing the propagation of damaged cells and suppressing tumor growth. Mutant p53 proteins can act as dominant negatives over wild-type p53 or gain novel oncogenic functions that drive cancer progression.

Clinical Research & Evidence

Inactivation of p53 allows cancer cells to proliferate uncontrollably, evade apoptosis, and acquire invasive and metastatic properties. Restoring p53 function is an active area of cancer research and therapy.

Primary Research Reference

Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024 Jun 10;42(6):946-967.

PMID: 38729160; PMCID: PMC11190820

Therapeutic Interventions

EGCG and p53 Stabilization

EGCG Mechanism

The interaction between EGCG and p53 preserves the protein against degradation. Both EGCG and MDM2 bind at the same place on p53, the N-terminal domain, so EGCG competes with MDM2. When EGCG binds with p53, the protein is not being degraded through MDM2, increasing p53 levels for anti-cancer function.

Zhao J, et al. Nat Commun. 2021 Feb 12;12(1):986. PMID: 33579943

Other Natural Compounds

Indole-3-carbinol

I3C Induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells. Reference

PEITC Treatment

In mutant-p53 cancers, PEITC restores WT-like function. Reference

Nutritional Factors

Zinc Deficiency Impact

Deficient zinc through competition with copper causes p53 to misfold, resulting in functional loss of transcriptional activity. Reference

Vitamin K Metabolism

Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism. Reference