Cholesterol modification of proteins

The demonstration over 30 years ago that inhibitors of cholesterol biosynth esis disrupt animal development suggested an intriguing connection between fundamental cellular metabolic processes and the more global processes of e mbryonic tissue patterning. Adding a new dimension to this relationship is the more recent finding that the Hedgehog family of tissue patterning facto rs are covalently modified by cholesterol. Here we review the mechanism of the Hedgehog autoprocessing reaction that results in this modification, and compare this reaction to that undergone by other autoprocessing proteins. We also discuss the biological consequences of cholesterol modification, in particular the use of cholesterol as a molecular handle in the spatial dep loyment of the protein signal in developing tissues. Finally, the developme ntal consequences of chemical and genetic disruption of cholesterol homeost asis are summarized, along with the potential importance of cholesterol-ric h lipid rafts: in production of and response to the Hh signal. (C) 2000 Els evier Science B.V. All rights reserved.