TY - JOUR
T1 - Identification of a novel TGF-β-regulated gene encoding a putative zinc finger protein in human osteoblasts
AU - Subramaniam, Malayannan
AU - Harris, Steven A.
AU - Oursler, Merry Jo
AU - Rasmussen, Kay
AU - Riggs, B. Lawrence
AU - Spelsberg, Thomas C.
N1 - Funding Information:
This work was supported by NIH grants AGO4875, AR4I652, and the Mayo Foundation. SH and MS were supported by NCI Training Grant CA90441. We would like to thank Dr Marian Young for the kind gift of human osteoblast cDNA library, Genetics Institute for providing the BMP-2, Drs Michael Getz and Eric Wieben for critically reviewing the manuscript, Dr G. S. Sandhu for analyzing the sequences in the GenBank, and Ms Jacquelyn House for her excellent clerical assistance.
PY - 1995
Y1 - 1995
N2 - The TGF-β family of growth factors has been extensively studied and found to play major roles in bone physiology and disease. A novel, TGF-β-inducible early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified using differential-display PCR. Using this differentially expressed cDNA fragment of TIEG to screen a hOB cDNA library, a near full-length cDNA for this gene was isolated. Northern analyses indicated that the steady-state levels of the 3.5 kb TIEG mRNA increased within 30 min of TGF-β treatment of human osteoblasts and reached a maximum of 10-fold above control levels at 120 min post-treatment. This regulation was independent of new protein synthesis. Computer sequence analyses indicates that TIEG mRNA encodes for a 480 amlnoacid protein. The TIEG protein contains three zinc finger motifs, several proline-rich src homology-3 (SH3) binding domains at the C-terminal end, and is homologous in this region to the zinc finger-containing transcription factor family of genes. A growth factor/cytokine-specific induction of TIEG has been shown. TIEG expression in hFOB cells was highly induced by TGF-β and bone morphogenetic protein-2 (BMP-2), with a moderate induction by epidermal growth factor (EGF), but no induction by other growth factors/cytokines was observed. In addition to osteoblastic cells, high levels of TIEG expression were detected in skeletal muscle tissue, while low or no detectable levels were found in brain, lung, liver or kidney. Because TIEG is an early induced putative transcription factor gene, and shows a growth factor induction and tissue specificity, its protein product might play an important role as a signalling molecule in osteoblastic cells.
AB - The TGF-β family of growth factors has been extensively studied and found to play major roles in bone physiology and disease. A novel, TGF-β-inducible early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified using differential-display PCR. Using this differentially expressed cDNA fragment of TIEG to screen a hOB cDNA library, a near full-length cDNA for this gene was isolated. Northern analyses indicated that the steady-state levels of the 3.5 kb TIEG mRNA increased within 30 min of TGF-β treatment of human osteoblasts and reached a maximum of 10-fold above control levels at 120 min post-treatment. This regulation was independent of new protein synthesis. Computer sequence analyses indicates that TIEG mRNA encodes for a 480 amlnoacid protein. The TIEG protein contains three zinc finger motifs, several proline-rich src homology-3 (SH3) binding domains at the C-terminal end, and is homologous in this region to the zinc finger-containing transcription factor family of genes. A growth factor/cytokine-specific induction of TIEG has been shown. TIEG expression in hFOB cells was highly induced by TGF-β and bone morphogenetic protein-2 (BMP-2), with a moderate induction by epidermal growth factor (EGF), but no induction by other growth factors/cytokines was observed. In addition to osteoblastic cells, high levels of TIEG expression were detected in skeletal muscle tissue, while low or no detectable levels were found in brain, lung, liver or kidney. Because TIEG is an early induced putative transcription factor gene, and shows a growth factor induction and tissue specificity, its protein product might play an important role as a signalling molecule in osteoblastic cells.
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U2 - 10.1093/nar/23.23.4907
DO - 10.1093/nar/23.23.4907
M3 - Article
C2 - 8532536
AN - SCOPUS:0028971148
SN - 0305-1048
VL - 23
SP - 4907
EP - 4912
JO - Nucleic acids research
JF - Nucleic acids research
IS - 23
ER -