Ets1 is an effector of the transforming growth factor beta (TGF-beta ) signaling pathway and an antagonist of the profibrotic effects of TGF-beta

The Journal of Biological Chemistry
Joanna Czuwara-LadykowskaMaria Trojanowska

Abstract

Extracellular matrix (ECM) production and turnover are tightly controlled under normal physiological conditions. Ets factors regulate matrix turnover by activating transcription of several metalloproteinases (MMPs) and are frequently overexpressed in aggressive tumors and arthritis. Because of the prominent role of transforming growth factor beta (TGF-beta) in ECM synthesis, this study was undertaken to determine the possible interactions between Ets1 and the TGF-beta pathway. Experiments using adenoviral delivery of Ets1 in human fibroblasts have established that Ets1 strongly suppresses TGF-beta induction of collagen type I and other matrix-related genes and reverses TGF-beta-dependent inhibition of MMP-1. Subsequent experiments utilizing COL1A2 promoter demonstrated that Ets1 in the presence of TGF-beta signaling interferes with the stimulatory role of p300. To gain further insight into the mechanism of Ets1 inhibition of the TGF-beta signaling, the protein levels and post-translational modifications of Ets1 after TGF-beta treatment were analyzed. The level of total Ets1 protein was not affected after 24 h of TGF-beta stimulation. Moreover, TGF-beta did not affect either serine or threonine phosphorylation levels of Ets1. Ho...Continue Reading

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