The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in clear cell renal cell carcinoma. Under normal oxygen conditions, the VHL protein functions as part of an E3 ubiquitin ligase complex that targets which transcription factor for proteasomal degradation?
- A Hypoxia-inducible factor 1-alpha (HIF-1alpha) ✓
- B MYC
- C p53
- D NF-kB
Correct answer: A. Hypoxia-inducible factor 1-alpha (HIF-1alpha)
Explanation
VHL ubiquitinates HIF-1alpha under normoxic conditions, targeting it for proteasomal degradation. Loss of VHL causes HIF-1alpha accumulation, driving transcription of VEGF, erythropoietin, and other pro-angiogenic genes. Option C is targeted by MDM2, not VHL. Option B is regulated by other mechanisms. Option D is regulated by IκB.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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