The present invention pertains to the modification of the eukaryotic ubiquitin system by using the bacterial virulence factor SdeA and variants and mutants thereof. The invention is based on the phosphodiesterase activity of SdeA, which catalyzes a phospho-ribosylation (or simply "ribosylation") event of ubiquitin and ubiquitin-like proteins. The invention provides SdeA proteins and mutants without said phosphodiesterase activity, as well as medical applications of these recombinant proteins, their encoding nucleic acids, ribosylated ubiquitin proteins, and compounds which may act as selective or non-selective phosphodiesterase inhibitors.
