Abstract |
In a subset of human lipomas, a specific t(3;12) chromosome translocation gives rise to HMGA2-LPP fusion protein, containing the amino (N)-terminal DNA binding domains of HMGA2 fused to the carboxyl (C)-terminal LIM domains of LPP. In addition to its role in adipogenesis, several observations suggest that HMGA2-LPP is linked to chondrogenesis. Here, we analyzed whether HMGA2-LPP promotes chondrogenic differentiation, a marker of which is transactivation of the alpha 2 type XI collagen gene (Col11a2). Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed. Luciferase assay demonstrated that either of HMGA2-LPP, wild-type HMGA2 or the N-terminal HMGA2 transactivated the Col11a2 promoter in HeLa cells, while the C-terminal LPP did not. RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion. These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains.
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Authors | Takahiro Kubo, Yoshito Matsui, Tomohiro Goto, Kiminori Yukata, Natsuo Yasui |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 340
Issue 2
Pg. 476-81
(Feb 10 2006)
ISSN: 0006-291X [Print] United States |
PMID | 16375854
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Collagen Type XI
- Cytoskeletal Proteins
- DNA-Binding Proteins
- HMGA2 Protein
- LIM Domain Proteins
- LPP protein, human
- Mutant Chimeric Proteins
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Topics |
- Binding Sites
(genetics)
- Chondrogenesis
(genetics)
- Collagen Type XI
(biosynthesis, classification, genetics)
- Cytoskeletal Proteins
(biosynthesis, genetics, physiology)
- DNA-Binding Proteins
(metabolism)
- Gene Expression Regulation, Neoplastic
(physiology)
- HMGA2 Protein
(biosynthesis, genetics, physiology)
- Humans
- LIM Domain Proteins
- Lipoma
(genetics, metabolism)
- Mutant Chimeric Proteins
(genetics, metabolism, physiology)
- Promoter Regions, Genetic
- Protein Structure, Tertiary
(genetics)
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