Note for: The Unusual Case of Porcupine
Note: The Unusual Case of Porcupine (doi:10.1126/science.1228179) Forward chemical genetics: Know the target of the chemical compound -- screening for the phenotype in cells Reverse chemical genetics: Know the protein target -- screening for the action of the chemical compound Wnt proteins is pivotal in animal development and tissue homeostasis, and has become a high-priority anticancer drug target given its essential role in colorectal cancer and its contribution to a broad range of other cancer types. Roel Nusse, Varmus linked deviant activity of Wnt molecules to cancer. LGK974—an acyltransferase called Porcupine (Porcn) that adds fatty acid to Wnt—has been well studied, few of the meeting participants were aware of the drug candidate. Discovered in screens for genes that affect embryonic patterning in the fruit fly, PORCN is the founding member of a 16-gene family with predicted acyltransferase activity. The fatty acyl modification of Wnt, Hedgehog, and...