Tumor protein p53 (TP53) and intrinsic apoptotic pathway components (p53/Intrinsic Apoptosis)

Tumor protein p53 (TP53) and the intrinsic apoptotic pathway components constitute a central mechanism for programmed cell death in response to cellular stress (UniProt: P04637). p53 acts as a master transcription factor that, upon activation by DNA damage or oncogenic stress, upregulates pro-apoptotic members of the Bcl-2 family, such as BAX, PUMA, and NOXA (Cell: 10.1016/S0092-8674(02)00657-5). These proteins facilitate mitochondrial outer membrane permeabilization (MOMP), leading to the release of cytochrome c and the subsequent activation of the caspase cascade, including Caspase-9 and Caspase-3 (StatPearls: NBK537209). In many cancers, this pathway is disabled through TP53 mutations or the overexpression of negative regulators like MDM2 or anti-apoptotic proteins like BCL-2 (Nature: 10.1038/35044018). Therapeutic strategies include MDM2 inhibitors to stabilize wild-type p53 and BH3 mimetics, such as Venetoclax, to directly trigger the intrinsic pathway by inhibiting BCL-2 family members (Nature Medicine: 10.1038/nm.3048).

Other names

p53 pathwayMitochondrial apoptotic pathwayTP53-mediated apoptosisBcl-2 family-regulated apoptosis

Stabilization of p53 via MDM2 antagonism and inhibition of anti-apoptotic BCL-2 family proteins to trigger mitochondrial outer membrane permeabilization (MOMP) and caspase activation (PubMed: 23396210; StatPearls: NBK537209).