A cultured fibroblast line is loaded with exogenous cholesterol until intracellular unesterified cholesterol is abundant. Which change in the SREBP pathway explains the fall in LDL receptor expression observed under these conditions?

• A SREBP-2 is ubiquitinated and degraded before reaching the Golgi
• B SREBP-2 remains anchored in the endoplasmic reticulum in complex with SCAP and Insig ✓
• C SREBP-2 translocates to the nucleus but is inactivated by acetylation
• D SREBP-2 is exported from the nucleus by CRM1-mediated nuclear export

Explanation

When membrane cholesterol is plentiful, cholesterol binds SCAP and promotes association of the SCAP-SREBP complex with Insig, an ER retention protein. Cleavage by site-1 and site-2 proteases in the Golgi therefore does not occur, no basic helix-loop-helix transcription factor reaches the nucleus, and transcription of the LDL receptor and HMG-CoA reductase genes falls. This coordinate suppression prevents both further uptake and further synthesis. Degradation, nuclear export, and acetylation are not part of the canonical sterol-sensing mechanism examined here.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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