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Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1

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Abstract

SIAH-1, an E3 ubiquitin ligase, plays an important role in regulating cell cycle, tumorigenesis and several neurodegenerative diseases. In this study, we found a novel SIAH-1-interacting protein, EEF1D (Eukaryotic translation elongation factor 1 delta). The interaction was confirmed in vitro and in vivo, and both proteins were co-localized in the cytoplasm. The Cys-rich domain of SIAH-1 was essential for its interaction with EEF1D. Overexpressing SIAH-1 had no effect on the protein level of EEF1D, implying that EFF1D is not the substrate of SIAH-1. In contrast, the protein level of SIAH-1 increased significantly in the cells overexpressing EEF1D. Increased amount of SIAH-1 was caused by the EEF1D-mediated inhibition of auto-ubiquitination and degradation of SIAH-1. Furthermore, EEF1D was able to inhibit the degradation of HPH2, a known substrate of SIAH-1. Taken together, our data suggest EFF1D functions as a novel negative regulator of SIAH-1.

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Acknowledgments

We are grateful to Yan-Hua Wu for critical reading of the manuscript. This study is supported by grants from the National Basic Research Program of China (2010CB912603), National Special Key Project of China (2008ZX10003-006 and 2009ZX09301-011) to K. Huo.

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Rd., Shanghai, 200433, People’s Republic of China

    Huiling Wu, Yan Shi, Ying Lin, Wei Qian & Keke Huo

  2. Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, 11794, USA

    Yao Yu

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  1. Huiling Wu
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  2. Yan Shi
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  3. Ying Lin
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  4. Wei Qian
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Correspondence to Keke Huo.

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Wu, H., Shi, Y., Lin, Y. et al. Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1. Mol Cell Biochem 357, 209–215 (2011). https://doi.org/10.1007/s11010-011-0891-5

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  • DOI: https://doi.org/10.1007/s11010-011-0891-5

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