Biological Actions of TIEG in Skeletal Cells

Dr. M. Subramaniam, Dr. John Hawse, and Kay Rasmuseen, funded by an NIH grant (DE14706), find that a TGF-β inducible early gene (TIEG), discovered by this laboratory, has been shown to code for a 3-zinc finger nuclear transcription factor which regulates the expression of certain Smad pathway genes in osteoblasts, osteosarcomas, and breast cancer cells. The overexpression of TIEG mimics the action of TGFβ in both osteoblasts and breast cancer cells. The functions of TIEG and its turnover by ubiquitin proteosomal pathway and the action of TIEG in repressing Smad-7 and inducing Smad-2 gene expression are under investigation in collaboration with the laboratory of Dr. Ralf Janknecht.

Furthermore, in this laboratory, TIEG knockout mice have been developed and are currently under examination for structural defects, as well as incidence of cancer in the aged mice. Both fibroblasts and osteoblast cells, derived from these mice, have demonstrated defects in cell proliferation.

Role of TIEG in the TGFB-Smad Signaling