The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor γ-Dependent Adipocyte Differentiation

• DOI: 10.1128/mcb.01001-08
• Publication Date: 2009-07-14T00:54:50Z
• Authors: Koen M. A. Dreije...; Radhika A. Varier; Olivier van Beekum; Ellen H. Jeninga; Jo W. M. Höppener; Cornelis J. M. Lips; J. Alain Kummer; Eric Kalkhoven; H. T. Marc Timmers
• Keywords: MEN1; Corepressor

Menin, the product of MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation gene transcription as part an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 histone H3 (H3K4). As patients frequently develop lipomas and peroxisome proliferator-activated receptor gamma (PPARgamma) expressed several MEN1-related types, we investigated regulation PPARgamma by menin. We found that menin required adipocyte differentiation murine 3T3-L1 cells PPARgamma-expressing mouse embryonic fibroblasts. Menin augments target expression through recruitment H3K4 activity. interacts directly with function 2 domain a ligand-independent fashion. Ligand-dependent coactivation, however, dependent on LXXLL motif intact helix 12 PPARgamma. propose important factor PPARgamma-mediated adipogenesis loss may contribute to lipoma development patients.