Determining how protection of ABCE1 contributes to maintenance of tumour growth: a structure and function approach.

Abstract

ORAOV1 is amplified in many solid tumours, driving tumour formation. The corresponding protein is part of a heterotrimeric complex in which an ABC type ATPase (ABCE1) is the catalytic centre.  There are numerous points of interaction between the members of this complex, presenting opportunities for pharmacological intervention designed to limit tumour growth.  To exploit this complex as a drug target, we will determine the 3D structure of the complex.  This will also lead to understanding a unique aspect of the complex, namely the role played by two of the proteins in protecting the reactive oxygen species-sensitive iron-sulfur cluster of ABCE1. 




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]

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[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  


Biological Areas:

Structural Biology
Genetics

BBSRC Area:

Molecules, cells and industrial biotechnology