The social life of ABC transporters

PhD ceremony: Mr. P. Meszaros, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: The social life of ABC transporters

Promotor(s): prof. D. Hoekstra

Faculty: Medical Sciences

Cancer is one of the most serious diseases in the developed countries and it is usually treated with chemotherapy. If not all of the tumor cells are eradicated, recurrence of the tumor and associated multidrug resistance are a huge problem for follow up therapy. Multidrug resistance is often caused by (over)expression of ABC transporters. Today we know that ABC transporters are multi-spanning membrane proteins with the ability to pump molecules of a large variety of structures out of the tumor cell. ABC transporters form one of the largest protein families and are present in all known organisms from bacteria to humans. These transporters are present in all pharmacological barriers in our body, where they determine pharmacokinetic and ADMET parameters of drugs, and in vitro drug-transporter interactions can predict the tissue distribution of drug candidates. ABC transporters do not only cause problems when they function well, but mutations or malfunctioning of the transporter proteins constitutes the basis of several diseases. The aim of this thesis was to study ABC transporter activity as a function of their molecular environment (e.g. raft or non-raft localization) in the lateral plane of the membrane.