A binding motif for Siah ubiquitin ligase

Colin M House, Ian J Frew, Huei-Luen Huang, Gerhard Wiche, Nadia Traficante, Edouard C Nice, Bruno Catimel, David D L Bowtell

Research output: Contribution to journalArticleResearchpeer-review

101 Citations (Scopus)

Abstract

The Drosophila SINA (seven in absentia) protein and its mammalian orthologs (Siah, seven in absentia homolog) are RING domain proteins that function in E3 ubiquitin ligase complexes and facilitate ubiquitination and degradation of a wide range of cellular proteins, including beta-catenin. Despite these diverse targets, the means by which SINASiah recognize substrates or binding proteins has remained unknown. Here we identify a peptide motif (RPVAxVxPxxR) that mediates the interaction of Siah protein with a range of protein partners. Sequence alignment and mutagenesis scanning revealed residues that are important to this interaction. This consensus sequence correctly predicted a high-affinity interaction with a peptide from the cytoskeletal protein plectin-1 (residues 95-117). The unusually high-affinity binding obtained with a 23-residue peptide (K(Dapp) = 29 nM with SINA) suggests that it may serve as a useful dominant negative reagent for SINASiah proteins.
Original languageEnglish
Pages (from-to)3101 - 3106
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
Publication statusPublished - 2003
Externally publishedYes

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