Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene encoding neurofibromin. Neurofibromin functions as a:

• A Serine-threonine kinase that phosphorylates and inactivates CDK4
• B Transcriptional repressor in the Hedgehog signaling pathway
• C E3 ubiquitin ligase promoting proteasomal degradation of beta-catenin
• D GTPase-activating protein (GAP) that accelerates RAS-GTP hydrolysis, acting as a tumor suppressor ✓

Explanation

Neurofibromin is a RAS-GAP (GTPase-activating protein) that catalyzes hydrolysis of RAS-GTP to RAS-GDP, thereby inactivating RAS. Loss-of-function mutations in NF1 lead to constitutively active RAS signaling (hyperactivation of MAP kinase and PI3K pathways), driving cell proliferation in neurofibromas and malignant peripheral nerve sheath tumors. CDK4 regulation is the function of p16/p14ARF. Hedgehog repression involves PTCH1. Beta-catenin degradation involves APC.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.