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

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.
AuthorsTakahiro Kubo, Yoshito Matsui, Tomohiro Goto, Kiminori Yukata, Natsuo Yasui
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 340 Issue 2 Pg. 476-81 (Feb 10 2006) ISSN: 0006-291X [Print] United States
PMID16375854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Collagen Type XI
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • HMGA2 Protein
  • LIM Domain Proteins
  • LPP protein, human
  • Mutant Chimeric Proteins
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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