| First Author | Dreijerink KM | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 18 | Pages | 5060-9 |
| PubMed ID | 19596783 | Mgi Jnum | J:152608 |
| Mgi Id | MGI:4359311 | Doi | 10.1128/MCB.01001-08 |
| Citation | Dreijerink KM, et al. (2009) The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates peroxisome proliferator-activated receptor gamma-dependent adipocyte differentiation. Mol Cell Biol 29(18):5060-9 |
| abstractText | Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in several MEN1-related tumor types, we investigated regulation of PPARgamma activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPARgamma-expressing mouse embryonic fibroblasts. Menin augments PPARgamma target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPARgamma in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPARgamma. We propose that menin is an important factor in PPARgamma-mediated adipogenesis and that loss of PPARgamma function may contribute to lipoma development in MEN1 patients. |
