Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 368, Issue 1-2, Pages 147-153Publisher
SPRINGER
DOI: 10.1007/s11010-012-1353-4
Keywords
Smad; Yeast two hybrid; CREBZF/Zhangfei; BMP
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Funding
- Tanzman Foundation
- National Research Foundation of Korea (NRF)
- Korean government (MEST) [2011-0001042]
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Smads are the secondary messengers of the transforming growth factor-beta (TGF-beta) signaling pathway. TGF-beta 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-beta signaling. The regulation of Smads in the TGF-beta 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 (bZIP) 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.
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