Meta-Biol

• Pathways

In addition to being modified by cholesterol at its C-terminal end, the N-terminal fragment of Hh (Hh-Np) is also palmitoylated by the O-acyltransferase HHAT (Pepinsky et al, 1998; Charmoun et al 2001; Chen et al, 2004; Hardy and Resh, 2007). HHAT-mediated palmitoylation of Hh can be recapitulated in vitro and in vivo, and the cholesterol- and palmitoyl-modified N-terminal fragment represents the predominant secreted form of Hh in vivo (Buglino and Resh, 2008; Buglino and Resh, 2010; Taipale et al, 2000). Mutation or depletion of the HHAT enzyme and mutation of the palmitoyl acceptor cysteine in Hh itself abrogates palmitoylation of the ligand and reduces Hh signaling (Chen et al, 2004; Chamoun et al, 2001; Pepinsky et al, 1998; Callier et al, 2014).