ATP Binding Cassette (ABC) transporters are primary active transporters. They transport a wide range of substrates (e.g. ions, peptides, amino acids, sugar, xenobiotics, etc.) and use the energy from ATP hydrolysis to translocate molecules across membranes against their chemical gradient. They play a major role in drug pharmacokinetics and cancer multidrug resistance. A body of evidence support the role of several ABC transporters in tumorigenesis. ABCB5, a member of the ABCB family also known as multidrug resistance (MDR) family, can be found, among other cellular types, in melanocytes in the basal layer of epidermis. ABCB5 plays a specific role in melanoma chemoresistance and tumor cells progression. There are several isoforms including ABCB5 full length, ABCB5β, ABCB5α and others small transcripts. This study focuses on the "half like" transporter ABCB5β and more precisely on its potential heterodimerization with other half-transporters of the B family. The ABCB5β heterodimerization with ABCB6 and ABCB9 was evaluated given the common points between theses transporters. ABCB5β and ABCB6 are both upregulated in melanoma, involved in multidrug resistance and related to some diseases such as dyschromatosis universalis hereditaria. ABCB9 and ABCB5β show a similar localization profile in testis. To determine whether these half transporters dimerize, the Nano Bioluminescence Resonance Energy Transfer (NanoBRET) method has been performed. The study revealed that ABCB5β heterodimerizes with ABCB6 and ABCB9. Furthermore, data also indicate that ABCB6 and ABCB9 can dimerize. This work shed some light on the biology of ABCB5, a little characterized ABC transporter.
|Date of Award||17 Jan 2019|
|Supervisor||Jean-Pierre Gillet (Supervisor)|
- ABCB family
- protein-protein interaction