Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 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 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.
Kubo
Takahiro
T
Department of Orthopaedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
Matsui
Yoshito
Y
Goto
Tomohiro
T
Yukata
Kiminori
K
Yasui
Natsuo
N
D001665:Binding Sites / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D024161:Collagen Type XI / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D060588:LIM Domain Proteins; D008067:Lipoma / Q000235:genetics / Q000378:metabolism; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics
D024161:Collagen Type XI; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; D060588:LIM Domain Proteins; C103594:LPP protein, human; D050506:Mutant Chimeric Proteins