Prolonged endoplasmic reticulum stress from accumulation of misfolded proteins can trigger apoptosis. Which transcription factor is the key mediator that drives apoptosis during the unfolded protein response when ER stress is severe and prolonged?

• A NF-kappaB
• B CHOP (GADD153) ✓
• C ATF6
• D XBP1

Explanation

CHOP (C/EBP homologous protein, also called GADD153) is the key pro-apoptotic transcription factor induced during severe ER stress. It promotes apoptosis by downregulating Bcl-2 and inducing death receptors. ATF6 and XBP1 are adaptive UPR sensors that enhance protein folding. NF-kappaB is a pro-inflammatory transcription factor, not the primary ER stress-induced apoptotic mediator.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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