Identification of a novel TGF-β-regulated gene encoding a putative zinc finger protein in human osteoblasts

Malayannan Subramaniam, Steven A. Harris, Merry Jo Oursler, Kay Rasmussen, B. Lawrence Riggs, Thomas C. Spelsberg

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4907-4912
Number of pages6
JournalNucleic acids research
Volume23
Issue number23
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Genetics

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