Porcupine

Porcupine (Porcn), a member of the membrane bound O-acyltransferase (MBOAT) family, and is required for Wnt secretion and signaling. MBOATs are further categorized into three subgroups based on their biochemical reactions: lipid biosynthesis, sterol acylation and acylation of secreted proteins/peptides, including the appetite stimulating peptide hormone ghrelin and the hedgehog (Hh) and Wnt morphogen families.MBOATs are predicted to have 8–12 transmembrane domains (TMDs) and localize in the protein secretory pathway. The endoplasmic recticulum resident enzyme, porcupine (PORCN) is essential for the palmitoleation of the Wnt ligands at the highly conserved serine residue 209 before their secretion.  Secreted Wnt proteins play key roles in embryonic development, tissue homoeostasis and stem cell self-renewal; among the 19 Wnt proteins encoded in humans, Wnt3a is the most extensively studied isoform.  An early report that PORCN palmitoylated Wnts at a cysteine residue in the N-terminal region (Cys77 in Wnt3a) has been shown to be erroneous. The membrane bound O-acyl transferase (MBOAT) PORCN has emerged as a molecular target of interest in the search for more clinical options to treat Wnt-driven cancers.

References

1.Ho SY,et al. Bioorg Med Chem Lett. 2015;25(23):5472–5476. 2.Masumoto N, et al. Biochem Soc Trans. 2015;43(2):246–252.