Identification and functional analysis of Zranb2 as a novel Smad-binding protein that suppresses BMP signaling
Autor: | Toru Fukuda, Shoichiro Kokabu, Hiroki Sasanuma, Seiya Suzuki, Shun-ichiro Iemura, Katsumi Yoneyama, Satoshi Ohte, Masashi Shin, Eijiro Jimi, Toru Natsume, Yukio Nakamura, Takenobu Katagiri |
---|---|
Rok vydání: | 2012 |
Předmět: |
animal structures
Transcription Genetic Molecular Sequence Data Smad Proteins Bone Morphogenetic Protein 4 SMAD Biology Bone morphogenetic protein Biochemistry Cell Line Mice Animals Humans SMAD binding Amino Acid Sequence Molecular Biology RNA-Binding Proteins Bone morphogenetic protein 10 DNA Cell Biology Molecular biology Protein Structure Tertiary BMPR2 embryonic structures Phosphorylation Signal transduction Nuclear localization sequence Signal Transduction |
Zdroj: | Journal of Cellular Biochemistry. 113:808-814 |
ISSN: | 0730-2312 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |