Much progress has been made in understanding TGF-β signaling and the roles of the Smad proteins in specific gene expression. A new review looks at the transcriptional activators involved in TGF-β signal transduction. In addition to covering Smads, Cook and Urrutia discuss the recently identified TGF-β-inducible early-response genes (TIEGs). TIEG1 and TIEG2 are transcription factors that contain three Sp1-like DNA binding Zn2+ fingers and are expressed in several organs including pancreas, prostate, and brain glia. Whereas Smad proteins are grouped according to their ability to activate or repress gene expression, the two TIEGs identified thus far only repress gene expression. The TIEG NH2-terminal region has three conserved motifs involved in repression, and four linker segments that separate the repressor motifs and the COOH-terminal DNA binding domain. Overexpression of TIEG1 in the pancreatic cell line PANC-1 leads to growth suppression and apoptosis. Similar overexpression of TIEG2 suppresses epithelial cell proliferation. Transgenic mice expressing TIEG2 exhibit increased pancreatic apoptosis and disorganized acinar cell organization--similar to the early pancreatic atrophy observed in TGF-β transgenic mice. It is unknown whether TIEGs bind to the TGF-β receptor, as has been demonstrated for Smad proteins, nor is it known whether TIEG1 and TIEG2 share redundant properties or have specific roles in TGF-β-mediated signaling.
Cook, T., and Urrutia, R. (2000) TIEG proteins join the Smads as TGF-β-regulated transcription factors that control pancreatic cell growth. Am. J. Physiol. Gastrointest. Liver Physiol. 278: 513-521. [Abstract] [Full Text]