A patient with MEN1 syndrome (menin mutation) develops primary hyperparathyroidism from parathyroid hyperplasia, pancreatic neuroendocrine tumours, and a pituitary adenoma. Menin normally functions as:
- A A cytoplasmic kinase inhibiting cyclin D1 to prevent G1-to-S cell cycle entry
- B A ubiquitin ligase targeting cyclin E for proteasomal degradation
- C A nuclear scaffold protein that represses JunD-mediated transcription and maintains histone H3K4 methylation via interaction with MLL complexes ✓
- D A GTPase-activating protein (GAP) for RAS, preventing constitutive MAPK activation
Correct answer: C. A nuclear scaffold protein that represses JunD-mediated transcription and maintains histone H3K4 methylation via interaction with MLL complexes
Explanation
Menin (encoded by MEN1 at 11q13) is a nuclear scaffold protein that acts as a tumour suppressor by interacting with the MLL histone methyltransferase complex to maintain activating H3K4me3 marks at tumour suppressor gene loci and by repressing JunD-driven transcription of proliferative genes. Loss of menin function (two-hit mechanism) leads to histone methylation defects and unrestrained JunD-driven cell proliferation in parathyroid, pituitary, and pancreatic islet cells. Menin is not a cytoplasmic kinase, ubiquitin ligase, or RAS GAP.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.