Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD
- PMID:15563473
- DOI: 10.1074/jbc.M408143200
Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, JunD
Abstract
Mice null for menin, the product of the multiple endocrine neoplasia type 1 (MEN1) gene, exhibit cranial and facial hypoplasia suggesting a role for menin in bone formation. We have shown previously that menin is required for the commitment of multipotential mesenchymal stem cells into the osteoblast lineage in part by interacting with the bone morphogenetic protein (BMP)-2 signaling molecules Smad1/5, and the key osteoblast transcriptional regulator, Runx2 (Sowa H., Kaji, H., Hendy, G. N., Canaff, L., Komori, T., Sugimoto, T., and Chihara, K. (2004) J. Biol. Chem. 279, 40267-40275). However, menin inhibits the later differentiation of committed osteoblasts. The activator protein-1 (AP-1) transcription factor, JunD, is expressed in osteoblasts and has been shown to interact with menin in other cell types. Here, we examined the consequences of menin-JunD interaction on osteoblast differentiation in mouse osteoblastic MC3T3-E1 cells. JunD expression, assessed by immunoblot, gradually increased during osteoblast differentiation. Stable expression of JunD enhanced expression of the differentiation markers, Runx2, type 1 collagen (COL1), and osteocalcin (OCN) and alkaline phosphatase (ALP) activity and mineralization. Hence, JunD promotes osteoblast differentiation. In MC3T3-E1 cells in which menin expression was reduced by stable menin antisense DNA transfection, JunD levels were increased. When JunD and menin were co-transfected in MC3T3-E1 cells, they co-immunoprecipitated. JunD overexpression increased the transcriptional activity of an AP-1 luciferase reporter construct, and this activity was reduced by co-transfection of menin. Therefore, JunD and menin interact both physically and functionally in osteoblasts. Furthermore, menin overexpression inhibited the ALP activity induced by JunD. In conclusion, the data suggest that menin suppresses osteoblast maturation, in part, by inhibiting the differentiation actions of JunD.
Similar articles
- Menin and bone metabolism.Kaji H.Kaji H.J Bone Miner Metab. 2012 Jul;30(4):381-7. doi: 10.1007/s00774-012-0355-3. Epub 2012 Apr 28.J Bone Miner Metab. 2012.PMID:22543820Review.
- Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2.Sowa H, Kaji H, Hendy GN, Canaff L, Komori T, Sugimoto T, Chihara K.Sowa H, et al.J Biol Chem. 2004 Sep 24;279(39):40267-75. doi: 10.1074/jbc.M401312200. Epub 2004 May 18.J Biol Chem. 2004.PMID:15150273
- Inactivation of menin, the product of the multiple endocrine neoplasia type 1 gene, inhibits the commitment of multipotential mesenchymal stem cells into the osteoblast lineage.Sowa H, Kaji H, Canaff L, Hendy GN, Tsukamoto T, Yamaguchi T, Miyazono K, Sugimoto T, Chihara K.Sowa H, et al.J Biol Chem. 2003 Jun 6;278(23):21058-69. doi: 10.1074/jbc.M302044200. Epub 2003 Mar 20.J Biol Chem. 2003.PMID:12649288
- Role of menin in bone development.Kaji H, Canaff L, Hendy GN.Kaji H, et al.Adv Exp Med Biol. 2009;668:59-67. doi: 10.1007/978-1-4419-1664-8_6.Adv Exp Med Biol. 2009.PMID:20175453
- Menin and TGF-beta superfamily member signaling via the Smad pathway in pituitary, parathyroid and osteoblast.Hendy GN, Kaji H, Sowa H, Lebrun JJ, Canaff L.Hendy GN, et al.Horm Metab Res. 2005 Jun;37(6):375-9. doi: 10.1055/s-2005-870152.Horm Metab Res. 2005.PMID:16001330Review.
Cited by
- The tumor suppressor RASSF10 is upregulated upon contact inhibition and frequently epigenetically silenced in cancer.Richter AM, Walesch SK, Würl P, Taubert H, Dammann RH.Richter AM, et al.Oncogenesis. 2012 Jun 25;1(6):e18. doi: 10.1038/oncsis.2012.18.Oncogenesis. 2012.PMID:23552700Free PMC article.
- Impaired transforming growth factor-β (TGF-β) transcriptional activity and cell proliferation control of a menin in-frame deletion mutant associated with multiple endocrine neoplasia type 1 (MEN1).Canaff L, Vanbellinghen JF, Kaji H, Goltzman D, Hendy GN.Canaff L, et al.J Biol Chem. 2012 Mar 9;287(11):8584-97. doi: 10.1074/jbc.M112.341958. Epub 2012 Jan 24.J Biol Chem. 2012.PMID:22275377Free PMC article.Clinical Trial.
- De novo transcriptome analysis and gene expression profiling of fish scales isolated from Carassius auratus during space flight: Impact of melatonin on gene expression in response to space radiation.Furusawa Y, Yamamoto T, Hattori A, Suzuki N, Hirayama J, Sekiguchi T, Tabuchi Y.Furusawa Y, et al.Mol Med Rep. 2020 Oct;22(4):2627-2636. doi: 10.3892/mmr.2020.11363. Epub 2020 Jul 28.Mol Med Rep. 2020.PMID:32945420Free PMC article.
- Menin and bone metabolism.Kaji H.Kaji H.J Bone Miner Metab. 2012 Jul;30(4):381-7. doi: 10.1007/s00774-012-0355-3. Epub 2012 Apr 28.J Bone Miner Metab. 2012.PMID:22543820Review.
- Multiple Endocrine Neoplasia Syndromes from Genetic and Epigenetic Perspectives.Khatami F, Tavangar SM.Khatami F, et al.Biomark Insights. 2018 Jul 2;13:1177271918785129. doi: 10.1177/1177271918785129. eCollection 2018.Biomark Insights. 2018.PMID:30013307Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials