Germline loss-of-function mutations in the SHH receptor gene PATCHED1 (PTCH1) produce basal cell naevus (Gorlin) syndrome. In the normal state, PTCH1 inhibits which intracellular transducer of the hedgehog pathway?

• A Notch intracellular domain
• B GLI1 activator directly
• C β-catenin
• D Smoothened (SMO) ✓

Explanation

In the resting state, PTCH1 in the membrane constitutively represses Smoothened, keeping GLI transcription factors inactive. When SHH binds PTCH1, repression is lifted, SMO signals, and GLI enters the nucleus. Loss of PTCH1 therefore mimics continuous SHH signalling, driving basal cell carcinomas and medulloblastomas. β-catenin belongs to the Wnt pathway and Notch cleavage to the Notch pathway, neither regulated by PTCH1.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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