CREBZF, a novel Smad8-binding protein

Abstract

Smads are the secondary messengers of the transforming growth factor-b (TGF-b) signaling pathway. TGF-b receptors phosphorylate the Receptor Smads (R-Smads) upon ligand binding; activated R-Smads translocate to the nucleus and function as transcription factors. Among the R-Smads, Smads 1, 5, and 8 mainly mediate signals in the bone morphogenetic proteins (BMPs) pathways, while Smads 2/3 mediate TGF-b signaling. The regulation of Smads in the TGF-b signal pathway has been well defined, but the relationship of Smads 1, 5, and 8 to the BMP pathways has been relatively understudied. To understand the specific regulation of BMP mediating Smads, we performed yeast two-hybrid screening using the Mad homology 2(MH2) domain of Smad8 as bait. In this screening, novel Smad-binding protein, CREBZF\-a basic region-leucine zipper (b ZIP) transcription factor\-was identified. The interaction of CREBZF and Smads 1, 5, and 8 was confirmed by immunoprecipitation in a human prostate cancer cell line. Overexpression of CREBZF inhibited the promoter activity of BMP response element and abolished the cell growth inhibition induced by BMP- 6. Thus, CREBZF inhibits the function of BMP-6 by interacting with Smads. The identification of this novel Smads-binding protein, among others will help us understand the modulation of BMP-signaling pathways. © 2012 Springer Science+Business Media, LLC.