The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). IpaH9.8 is a bacterial E3 ligase and cloning of the gene from Shigella flexineri was first described by Demers et al. (1998). The IpaH family of proteins contain highly conserved leucine-rich repeats (LRR) in the amino-terminal region while the conserved carboxy-terminal regions possess E3 ligase activity (Rohde et al., 2007). The crystal structure of the IpaH protein has recently been described and based on this the IpaH family has been identified as a new class of E3 ubiquitin ligases found in pathogenic and symbiotic bacteria (Singer et al., 2008; Zhu, et al., 2008). IpaH9.8 has been shown to regulate the pheromone response by ubiquitylation and degradation of the MAPK kinase Ste7 (Rohde et al., 2007). IpaH9.8 has also been shown to inhibit NF-κB-dependent gene expression and the activity of U2AF35, an alternative splicing factor involved in host inflammatory responses (Haraga and Miller 2003).
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