Líffræðifélag Íslands
Líffræðiráðstefnan 2015

Erindi/veggspjald / Talk/poster V85

The role of V-ATPases in melanoma and their regulation by MITF

Sara Sigurbjörnsdóttir (1), Katrín Möller (1), Vésteinn Þórsson (2), Margrét Helga Ögmundsdóttir (1) og Eiríkur Steingrímsson (1)

1. Department of Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 2. Institute for Systems Biology, Seattle, USA.

Kynnir / Presenter: Sara Sigurbjörnsdóttir

Tengiliður / Corresponding author: Sara Sigurbjörnsdóttir (sas4@hi.is)

The vacuolar (H+)-ATPases (V-ATPases) are highly conserved multisubunit membrane-bound protein complexes that drive proton gradients across membranes. Their primary role is to create and maintain appropriate acidity of both intracellular compartments and extracellular space. Because the acidification of these compartments is critical for many biological processes, including membrane trafficking, protein degradation and cancer cell invasion, regulation of V-ATPase activity is of crucial importance. Recently, the melanoma oncogene Microphthalmia-associated transcription factor (MITF) was shown to induce the expression of all subunits of the V-ATPase in Drosophila, leading to increase in V-ATPase activity. Interestingly, MITF also regulates the expression of V-ATPases in human melanoma cells, suggesting that MITF can function as a master regulator of the V-ATPases. We aim to further explore the relationship between the MITF family and V-ATPases in the development of melanocytes as well as melanoma cells. We will determine how MITF regulates the expression of the different V-ATPase subunits in different cell types and determine their role in cancer development. The information gained will provide valuable insights into these highly conserved molecular systems and their contribution to cancer and may lead to novel insights into how to target this disease with drugs.