In neurofibromatosis type 1 (NF1), the NF1 gene product neurofibromin functions as:

• A A transcription factor activating tumor suppressor gene expression
• B A cell cycle checkpoint kinase inhibiting CDK4 activity
• C A nuclear envelope protein regulating chromatin organization
• D A GTPase-activating protein (GAP) that promotes GTP hydrolysis of RAS, downregulating RAS activity ✓

Explanation

Neurofibromin, the NF1 gene product, is a RAS-GTPase-activating protein (RAS-GAP) that normally promotes hydrolysis of active RAS-GTP to inactive RAS-GDP, thereby downregulating RAS/MAPK signaling. Loss of neurofibromin (two-hit) results in constitutive RAS activation and uncontrolled cell proliferation, predisposing to neurofibromas, optic gliomas, and plexiform neurofibromas. This is analogous to how KRAS mutations (resistant to GAP-mediated hydrolysis) drive pancreatic cancer.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.