Determining how a novel complex promotes tumour growth, by protecting an iron-sulphur cluster from cancer-associated oxidative stress.

Barry Panaretou (primary)
Institute of Pharmaceutical Science
King's College London
Annalisa Pastore (secondary)
Institute of Psychiatry, Psychology and Neuroscience
King's College London

Abstract

Solid tumours generate elevated levels of reactive oxygen species (ROS), that should compromise their ability to grow. Iron-sulphur clusters, essential cofactors for numerous proteins, are particularly ROS-labile. Until recently, strategies cancer cells evolve to limit damage to Fe-S clusters remain characterized. We have identified a heterodimeric complex protecting the Fe-S cluster located at the N terminus of ABCE1, an enzyme crucial for ribosome biogenesis and function (1). Not surprisingly, one of the members of this complex is overexpressed in many solid tumours. To exploit this complex as a drug target, we aim to understand how the complex protects iron-sulphur clusters.


References

1. Zhai C, Li Y, Mascarenhas C, Lin Q, Li K, Vyrides I, Grant CM, Panaretou B. (2014) The function of ORAOV1/LTO1, a gene that is overexpressed frequently in cancer: essential roles in the function and biogenesis of the ribosome. Oncogene 33: 484

2. Popovic M, Sanfelice D, Pastore C, Prischi F, Temussi PA and Pastore A (2015) Selective observation of the disordered import signal of a globular protein by in-cell NMR: the example of frataxins. Protein Science 24: 996

3. Prischi F, Konarev PV, Iannuxxi C, Pastore C, Adiunolfi S, Martin SR, Svergun DI and Pastore A (2010) Structural bases for the interaction of frataxin with the central components of iron-sulphur cluster assembly. Nature Communications 19: 95


BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsGeneticsMicroscopy / ElectrophysiologyMolecular Biology