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CREBZF, a novel Smad8-binding protein

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Abstract

Smads are the secondary messengers of the transforming growth factor-β (TGF-β) signaling pathway. TGF-β 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-β signaling. The regulation of Smads in the TGF-β 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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Acknowledgments

This study was supported in part by generous grants from the Tanzman Foundation and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2011-0001042).

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Authors and Affiliations

  1. Section of Urologic Oncology and the Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey and Robert Wood Johnson Medical School, 195 Little Albany Street #4560, New Brunswick, NJ, 08903, USA

    Jae-Ho Lee, Geun Taek Lee, Seok Joo Kwon, Jeongyun Jeong, Yun-Sok Ha & Isaac Yi Kim

  2. Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea

    Wun-Jae Kim

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  1. Jae-Ho Lee
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Correspondence to Isaac Yi Kim.

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Lee, JH., Lee, G.T., Kwon, S.J. et al. CREBZF, a novel Smad8-binding protein. Mol Cell Biochem 368, 147–153 (2012). https://doi.org/10.1007/s11010-012-1353-4

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