p53 responds to DNA damage by arresting the cell cycle, but if the damage is extensive it promotes apoptosis. Which transcriptional target of p53 is a BH3-only protein that directly activates the intrinsic apoptotic pathway?

• A XIAP
• B MDM2
• C Survivin
• D PUMA ✓

Explanation

PUMA (p53 upregulated modulator of apoptosis) and NOXA are BH3-only genes induced by p53 after irreparable DNA damage. Their protein products neutralize anti-apoptotic BCL-2 family members and activate BAX and BAK, committing the cell to mitochondrial apoptosis. MDM2 is a negative regulator that ubiquitinates p53 itself, forming an autoregulatory loop. Survivin and XIAP are inhibitors of apoptosis proteins that block executioner caspases and are not p53-induced pro-apoptotic mediators.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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