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Identification and functional analysis of Zranb2 as a novel Smad‐binding protein that suppresses BMP signaling
Author(s) -
Ohte Satoshi,
Kokabu Shoichiro,
Iemura Shunichiro,
Sasanuma Hiroki,
Yoneyama Katsumi,
Shin Masashi,
Suzuki Seiya,
Fukuda Toru,
Nakamura Yukio,
Jimi Eijiro,
Natsume Toru,
Katagiri Takenobu
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23408
Subject(s) - smad , bone morphogenetic protein , microbiology and biotechnology , zinc finger , gene knockdown , chemistry , c2c12 , phosphorylation , fanca , bone morphogenetic protein 10 , bone morphogenetic protein 2 , signal transduction , hek 293 cells , biology , bone morphogenetic protein 7 , transcription factor , myocyte , biochemistry , in vitro , dna , receptor , gene , myogenesis , fanconi anemia , dna repair
Smads 1/5/8 transduce the major intracellular signaling of bone morphogenetic proteins (BMPs). In the present study, we analyzed Smad1‐binding proteins in HEK293T cells using a proteomic technique and identified the protein, zinc‐finger, RAN‐binding domain‐containing protein 2 (ZRANB2). Zranb2 interacted strongly with Smad1, Smad5, and Smad8 and weakly with Smad4. The overexpression of Zranb2 inhibited BMP activities in C2C12 myoblasts in vitro , and the injection of Zranb2 mRNA into zebrafish embryos induced weak dorsalization. Deletion analyses of Zranb2 indicated that the serine/arginine‐rich (SR) domain and the glutamine‐rich domain were required for the inhibition of BMP activity and the interaction with Smad1, respectively. Zranb2 was found to be localized in the nucleus; however, the SR domain‐deleted mutant localized to the cytoplasm. The knockdown of endogenous Zranb2 in C2C12 cells enhanced BMP activity. Zranb2 suppressed Smad transcriptional activity without affecting Smad phosphorylation, nuclear localization, or DNA binding. Taken together, these findings suggested that Zranb2 is a novel BMP suppressor that forms a complex with Smads in the nucleus. J. Cell. Biochem. 113: 808–814, 2012. © 2011 Wiley Periodicals, Inc.