title: Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1.
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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.forename: Keke
authors.initials: K
authors.lastname: Huo
mesh_terms: D003545:Cysteine / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D059748:Proteolysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; C485977:PHC2 protein, human; D020648:Peptide Elongation Factor 1; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D003545:Cysteine