PMID- 19596783 OWN - NLM STAT- MEDLINE DCOM- 20090915 LR - 20211020 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 29 IP - 18 DP - 2009 Sep TI - The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates peroxisome proliferator-activated receptor gamma-dependent adipocyte differentiation. PG - 5060-9 LID - 10.1128/MCB.01001-08 [doi] AB - 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. FAU - Dreijerink, Koen M A AU - Dreijerink KM AD - University Medical Center Utrecht, Department of Physiological Chemistry, Utrecht, The Netherlands. FAU - Varier, Radhika A AU - Varier RA FAU - van Beekum, Olivier AU - van Beekum O FAU - Jeninga, Ellen H AU - Jeninga EH FAU - Hoppener, Jo W M AU - Hoppener JW FAU - Lips, Cornelis J M AU - Lips CJ FAU - Kummer, J Alain AU - Kummer JA FAU - Kalkhoven, Eric AU - Kalkhoven E FAU - Timmers, H T Marc AU - Timmers HT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090713 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (FABP4 protein, human) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (Histones) RN - 0 (Ligands) RN - 0 (MEN1 protein, human) RN - 0 (Men1 protein, mouse) RN - 0 (PPAR gamma) RN - 0 (Proto-Oncogene Proteins) RN - K3Z4F929H6 (Lysine) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*cytology/*metabolism MH - Animals MH - *Cell Differentiation MH - Fatty Acid-Binding Proteins/genetics MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Histones/metabolism MH - Humans MH - Ligands MH - Lysine/metabolism MH - Methylation MH - Mice MH - PPAR gamma/chemistry/*metabolism MH - Protein Binding MH - Protein Structure, Tertiary MH - Proto-Oncogene Proteins/*metabolism MH - Transcription, Genetic PMC - PMC2738285 EDAT- 2009/07/15 09:00 MHDA- 2009/09/16 06:00 PMCR- 2010/03/01 CRDT- 2009/07/15 09:00 PHST- 2009/07/15 09:00 [entrez] PHST- 2009/07/15 09:00 [pubmed] PHST- 2009/09/16 06:00 [medline] PHST- 2010/03/01 00:00 [pmc-release] AID - MCB.01001-08 [pii] AID - 1001-08 [pii] AID - 10.1128/MCB.01001-08 [doi] PST - ppublish SO - Mol Cell Biol. 2009 Sep;29(18):5060-9. doi: 10.1128/MCB.01001-08. Epub 2009 Jul 13.