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). Triad Domain-Containing Protein 1 (TRIAD1) is a member of the E3 protein ligase family and cloning of the human gene was first described by van der Reijden et al. (1999). TRIAD1 contains a TRIAD motif containing two RING domains which flank a conserved cysteine-rich (C6HC) domain designated DRIL (double RING finger-linked domain) (Marteijn et al., 2005). TRIAD is thought to be involved in protein translation, interacting with UbcH7 (UBE2L3) to polyubiquitylate eIF4E2 targeting it for proteasomal degradation (Tan et al., 2003). More recently these proteins have been referred to as Ring in-between Ring E3 ligases (RBRs) that function like RING-HECT hybrids regulating processes such as translation and immune signalling (Wenzel et al., 2011).
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Tan NG, Ardley HC, Scott GB, Rose SA, Markham AF, Robinson PA (2003) Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP. FEBS Lett 554, 501-4.
van der Reijden BA, Erpelinck-Verschueren CA, Lowenberg B, Jansen JH (1999) TRIADs: a new class of proteins with a novel cysteine-rich signature. Protein Sci 8, 1557-61.
Wenzel DM, Lissounov A, Brzovic PS, Klevit RE (2011) UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474, 105-8.