PMAIP1

PMAIP1, also known as Noxa, is a human gene that encodes a small pro-apoptotic protein of the Bcl-2 family. Noxa is a BH3-only member that promotes programmed cell death by antagonizing anti-apoptotic proteins and facilitating mitochondrial outer membrane permeabilization.

Expression of PMAIP1 is rapidly upregulated in response to cellular stress, most notably by the tumor suppressor p53 following DNA damage or oncogenic stress. Additional regulatory inputs include endoplasmic reticulum stress pathways, where CHOP can contribute to Noxa induction. In unstressed cells, PMAIP1 transcripts are relatively low, but can be induced in a tissue-specific manner under stress.

Biochemically, Noxa binds selectively to anti-apoptotic Bcl-2 family members such as Mcl-1 and A1/Bfl-1. This interaction neutralizes their inhibition of Bax and Bak, enabling Bax/Bak activation, mitochondrial outer membrane permeabilization, cytochrome c release, and activation of caspases that execute apoptosis. Because of its selective targeting of Mcl-1–dependent survival pathways, Noxa often functions to modulate cellular sensitivity to DNA-damaging agents and other stresses.

In humans, PMAIP1/Noxa participates in p53-dependent and -independent apoptotic programs and has been implicated in tumor suppression, immune responses, and responsiveness to chemotherapy. The gene is studied as a potential contributor to cancer therapy efficacy and as part of the broader p53-mediated apoptosis network.

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