Loss-of-function mutations of the APC gene initiate most sporadic colorectal adenomas. The direct biochemical consequence of APC loss that drives proliferation is:

• A Accumulation of GSK-3beta, which constitutively phosphorylates and activates glycogen synthase
• B Accumulation of beta-catenin, which translocates to the nucleus and upregulates MYC and cyclin D1 transcription ✓
• C Degradation of E-cadherin, releasing free cytoplasmic catenins that activate TGF-beta receptors
• D Accumulation of axin, which inhibits the MAP kinase cascade downstream of RAS

Explanation

APC is part of the destruction complex with axin and GSK-3beta that phosphorylates beta-catenin, targeting it for ubiquitin-mediated proteasomal degradation. When APC is lost, beta-catenin escapes degradation, accumulates, enters the nucleus and partners with TCF to drive transcription of MYC and cyclin D1. GSK-3beta remains present but inactive against beta-catenin, killing option A.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.