Protein Prenylation: the Anchor of Life


What is Protein Prenylation?

Protein prenylation is a post-translational modification that consists of the attachment of 15 or 20 carbon isoprenoids to specific cysteine residues positioned near the C-termini of proteins.  In a eukaryotic cell, there are several hundred prenylated proteins including most members of the Ras superfamily and heterotrimeric G-proteins; the prenyl group serves to anchor these proteins in the membrane so that they are positioned to interact with cell surface receptors either directly or via adaptor proteins.  This means that essentially all signaling processes in eukaryotic cells require the participation of prenylated proteins for everything ranging from the regulation of cell division to stem cell differentiation and development.  Beyond biological significance, the critical role of prenylated proteins also makes them important targets for the design of new therapeutic agents for a variety of diseases


Research in the Distefano Group

Work in the Distefano Group on protein prenylation is focused in two areas: Chemical Biology and Biotechnology Applications.  In pursuit of those studies, members of the group perform a variety of different types of experiments including chemical synthesis, biochemistry, proteomics and cell culture and animal-based work.  The goal of this work is to gain insight into protein prenylation that can be used to advance biology and develop new therapeutic approaches for a broad range of diseases including cancer, Alzheimer’s disease and infectious disease.

Group News

Red-shifted backbone N–H photocaging agents

In a recent article published in Organic and Biomolecular Chemistry, graduate student Taysir Bader, in the research group of Professor Mark Distefano, in collaboration with graduate student Alicia E. Mangubat-Medina, and undergraduates Hallie O. Trial, Reyner D. Vargas, and Mekedlawit T. Setegne in the research group of Dr.

Specific RNA splicing inhibitors lead to cancer reduction

In reseach recently published in the Proc. Nat. Acad. Sci. U.S.A., graduate student Kiall Suazo in the Distefano Lab contributed to a collaborative project led by Professor Carol Williams in Medical College of Wisconsin in altering SmgGDS ratios using splice-switching strategy. SmgGDS has two isoforms (SmgGDS-607 and SmgGDS-558) that work together in prenylating and subsequent trafficking of a set of small GTPases.

Former Postdoc Matt Hammers Starts Faculty Position at UW LaCrosse

Former Distefano group postdoc Matt Hammers started his independent career as a Professor at University of Wisconsin La Crosse this fall.  In the Distefano group, Matt worked on the development of new photoremovable protecting groups for cysteine and their use for biological experiments including the uncaging of peptides and drugs inside cells.