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Negative regulation of BMP/Smad signaling by Tob in osteoblasts.
- Source :
-
Cell [Cell] 2000 Dec 22; Vol. 103 (7), pp. 1085-97. - Publication Year :
- 2000
-
Abstract
- Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.
- Subjects :
- Alleles
Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 7
Bone Remodeling physiology
Cell Differentiation physiology
Cell Division physiology
Cell Size physiology
Gene Expression physiology
Germ-Line Mutation physiology
Intracellular Signaling Peptides and Proteins
Ligands
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoblasts cytology
Phosphoproteins metabolism
Skull cytology
Smad Proteins
Smad1 Protein
Smad5 Protein
Smad8 Protein
Transcription, Genetic physiology
Bone Morphogenetic Proteins metabolism
Carrier Proteins genetics
Carrier Proteins metabolism
DNA-Binding Proteins metabolism
Osteoblasts physiology
Signal Transduction physiology
Trans-Activators metabolism
Transforming Growth Factor beta
Subjects
Details
- Language :
- English
- ISSN :
- 0092-8674
- Volume :
- 103
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 11163184
- Full Text :
- https://doi.org/10.1016/s0092-8674(00)00211-7