A 40-year-old woman with a familial syndrome develops multiple osteomas, epidermoid cysts, supernumerary teeth, and is found on colonoscopy to have hundreds of colonic polyps. Genetic testing reveals an APC gene truncating mutation. The APC protein normally functions by:

• A Binding RAS to prevent downstream MAPK signaling
• B Promoting ubiquitin-mediated proteasomal degradation of β-catenin in the cytoplasm ✓
• C Competing with SMAD4 for binding to TGF-β receptor complexes
• D Directly acetylating histone H3K27 to silence Wnt target genes

Explanation

This is Familial Adenomatous Polyposis (FAP) / Gardner syndrome. APC is a key component of the β-catenin destruction complex (with Axin, GSK-3β, and CK1). In cells without active Wnt signaling, APC facilitates phosphorylation of β-catenin by GSK-3β, targeting it for ubiquitination (via β-TrCP E3 ligase) and proteasomal degradation, thereby suppressing Wnt/β-catenin target gene transcription. When APC is mutated/absent, β-catenin accumulates, translocates to the nucleus, and activates proliferative genes (cyclin D1, MYC), driving adenoma formation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.