Background
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). WW domain containing Protein (WWP1) is a member of the E3 protein ligase family and cloning of the human gene was first described by Pirozzi et al. (1997). WWP1 belongs to the NEDD4 protein family and contains 4 WW domains (Flasza et al., 2002; Pirozzi et al., 1997). The intrinsic E3 ligase activity of WWP1 is conferred through a HECT domain at the C-terminus of the protein (Pirozzi et al., 1997). WWP1 has been shown to interact with Smad7 in human epithelial cell lines to cause the ubiquitylation and degradation of Transforming Growth Factor Beta Receptor-1 (TGFβR-1) (Seo et al., 2004). Treatment of human embryonic kidney cells with TGFβ also leads to the ubiquitylation and degradation of SMAD2 through the interaction of SMAD2/SMAD3, and the nuclear co-repressor Transforming Growth Factor Beta-Induced Factor (TGIF) with WWP1 (Seo et al., 2004).
References
Flasza M, Gorman P, Roylance R, Canfield AE, Baron M (2002) Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein. Biochem Biophys Res Commun 290, 431-7.
Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM (1997) Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem 272, 14611-6.
Seo SR, Lallemand F, Ferrand N, Pessah M, L'Hoste S, Camonis J, Atfi A (2004) The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. EMBO J 23, 3780-92.