Cholesterol regulates its own biosynthesis through the SREBP pathway. When intracellular sterol levels are low, which sequence correctly describes the regulatory response?

• A SREBP activates translation of HMG-CoA reductase mRNA without entering the nucleus
• B Insig binds SCAP and permits transport of SREBP to the nucleus
• C SREBP is ubiquitinated and degraded by the proteasome, lowering HMG-CoA reductase transcription
• D SCAP escorts SREBP from the endoplasmic reticulum to the Golgi, where site-1 and site-2 proteases release the active transcription factor ✓

Explanation

In low sterol states, Insig dissociates from the SCAP-SREBP complex, allowing SCAP to carry SREBP to the Golgi. Site-1 protease and site-2 protease sequentially release the basic helix-loop-helix domain, which enters the nucleus and upregulates HMG-CoA reductase, LDL receptor, and other genes. Option B reverses the role of Insig, which anchors the complex in the ER only when sterols are abundant.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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