PMID- 15563473
OWN - NLM
STAT- MEDLINE
DCOM- 20050405
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 6
DP  - 2005 Feb 11
TI  - Menin suppresses osteoblast differentiation by antagonizing the AP-1 factor, 
      JunD.
PG  - 4785-91
AB  - 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.
FAU - Naito, Junko
AU  - Naito J
AD  - Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, 
      Department of Clinical Molecular Medicine, Kobe University Graduate School of 
      Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
FAU - Kaji, Hiroshi
AU  - Kaji H
FAU - Sowa, Hideaki
AU  - Sowa H
FAU - Hendy, Geoffrey N
AU  - Hendy GN
FAU - Sugimoto, Toshitsugu
AU  - Sugimoto T
FAU - Chihara, Kazuo
AU  - Chihara K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041123
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BMP2 protein, human)
RN  - 0 (Bmp2 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transforming Growth Factor beta)
RN  - 63231-63-0 (RNA)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Proteins/metabolism
MH  - Cell Differentiation
MH  - Cell Line
MH  - DNA, Complementary/metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Luciferases/metabolism
MH  - Mice
MH  - Oligonucleotides, Antisense/chemistry
MH  - Osteoblasts/*cytology/metabolism
MH  - Plasmids/metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/*chemistry/*physiology
MH  - Proto-Oncogene Proteins c-jun/metabolism/*physiology
MH  - RNA/chemistry
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Transcription Factor AP-1/*metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2004/11/26 09:00
MHDA- 2005/04/06 09:00
CRDT- 2004/11/26 09:00
PHST- 2004/11/26 09:00 [pubmed]
PHST- 2005/04/06 09:00 [medline]
PHST- 2004/11/26 09:00 [entrez]
AID - S0021-9258(20)76128-4 [pii]
AID - 10.1074/jbc.M408143200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Feb 11;280(6):4785-91. doi: 10.1074/jbc.M408143200. Epub 2004 
      Nov 23.