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

Jeff Vervacke defends Ph.D. thesis

On Thursday 5/5, Jeff Vervacke defended his thesis entitled "Small Molecules and Functionalized Peptides to Study Protein Prenylation".  In the course of his Ph.D. work, Jeff has worked on a wide range of peptide-related projects.  Beyond his work on protein prenylation, Jeff has also worked on the preparation of peptides for vaccine development and for the study of DNA repair.

Mohsen Mahmoodi's paper on NDBF thiol protection accepted in JACS

Graduate student Mohsen Mahmoodi's paper titled "Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides" was accepted in the Journal of the American Chemical Society.  This manuscript describes the use of NDBF protection for thiols to allow one- and two photon uncaging of peptides to be performed in vitro and in live cells.  This allows thiol mediated events to be rapidly triggered with high efficiency.

Kevin Park attends retreat on cell durotaxis

Graduate student Kevin Park attended a retreat sponsored by Professor David Odde to discuss their NCI-funded project on Modeling and Microsystems Approach to Glioma Cell Migration.  The Distefano group is collaborating on this project by developing photochemical methods to control surface stiffness that can be used to study how cancer cells migrate on surfaces of varying stiffness.