Overexpression of HMGA2-LPP fusion transcripts promotes expression of the α 2 type XI collagen gene

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 sugg...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-02, Vol.340 (2), p.476-481
Main Authors: Kubo, Takahiro, Matsui, Yoshito, Goto, Tomohiro, Yukata, Kiminori, Yasui, Natsuo
Format: Article
Language:English
Subjects:
Adipogenesis
Binding Sites - genetics
Chondrogenesis
Chondrogenesis - genetics
Chromosomal translocation
COL11A2
Collagen Type XI - biosynthesis
Collagen Type XI - classification
Collagen Type XI - genetics
Cytoskeletal Proteins - biosynthesis
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - physiology
DNA-Binding Proteins - metabolism
Gene Expression Regulation, Neoplastic - physiology
HMGA2 Protein - biosynthesis
HMGA2 Protein - genetics
HMGA2 Protein - physiology
HMGA2-LPP
Humans
LIM Domain Proteins
Lipoma
Lipoma - genetics
Lipoma - metabolism
Mutant Chimeric Proteins - genetics
Mutant Chimeric Proteins - metabolism
Mutant Chimeric Proteins - physiology
Promoter Regions, Genetic
Protein Structure, Tertiary - genetics
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Summary: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 α 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.12.042