Neurofibromatosis type 1 (NF1) involves mutation of the NF1 gene encoding neurofibromin. Neurofibromin functions as a tumor suppressor through which mechanism?

• A Activating the retinoblastoma protein to arrest the cell cycle at G1/S checkpoint
• B Promoting p53-mediated apoptosis in cells with DNA damage
• C Acting as a GTPase-activating protein (GAP) that accelerates RAS inactivation ✓
• D Inhibiting mTOR signaling by activating TSC1/TSC2 complex

Explanation

Neurofibromin (NF1 protein) is a RAS-GTPase activating protein (RAS-GAP) that accelerates the intrinsic GTPase activity of RAS, converting active RAS-GTP to inactive RAS-GDP. Loss of neurofibromin leads to sustained RAS activation and downstream MAPK/PI3K signaling, promoting cell proliferation. This explains the predisposition to neurofibromas, Lisch nodules, and malignant peripheral nerve sheath tumors. TSC1/TSC2 suppression of mTOR is the tuberous sclerosis mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.