TIEG proteins join the Smads as TGF-beta-regulated transcription factors that control pancreatic cell growth

The control of epithelial cell proliferation, differentiation, and apoptosi s requires a balance between signaling and transcriptional regulation. Rece nt developments in pancreatic cell research have revealed that transforming growth factor-beta (TGF-beta) signaling is important for the regulation of each of these phenomena. More importantly, perturbations in this pathway a re associated with pancreatic cancer. A chief example of these alterations is the mutation in the TGF-beta-regulated transcription factor Smad4/DPC4 t hat is found in a large percentage of pancreatic tumors. Surprisingly, stud ies on transcription factors have remained an underrepresented area of panc reatic research. However, the discovery of Smad4/DPC4 as a transcription fa ctor fueled further studies aimed at characterizing transcription factors i nvolved in normal and neoplastic pancreatic cell growth. Our laboratory rec ently described the existence of a novel family of zinc finger transcriptio n factors, TGF-beta-inducible early-response gene (TIEG)1 and TIEG2, from t he exocrine pancreas that, similarly to Smads, participate in the TGF-beta response and inhibit epithelial cell proliferation. This review therefore f ocuses on describing the structure and function of these two families of tr anscription factor proteins that are becoming key players in the regulation of pancreatic cell growth.