Imperial College London
Dr David Pitcher

Dr David Pitcher

Central Faculty, Enterprise

Imperial College Advanced Hackspace Fellow
 
 
 
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Contact

 

d.pitcher

 
 
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Location

 

123Stadium HouseWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pitcher:2015,
author = {Pitcher, DS and de, Mattos-Shipley K and Tzortzis, K and Auner, HW and Karadimitris, A and Kleijnen, MF},
journal = {EBioMedicine},
pages = {642--648},
title = {Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure},
url = {http://hdl.handle.net/10044/1/23496},
volume = {2},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM). Bortezomib inhibits protein degradation by inactivating proteasomes’ active-sites. MM cells are exquisitely sensitive to Bortezomib - exhibiting a low-nanomolar IC50 - suggesting that minimal inhibition of degradation suffices to kill MM cells. Instead, we report, a low Bortezomib concentration, contrary to expectation, achieves severe inhibition of proteasome activity in MM cells: the degree of inhibition exceeds what one would expect from the small proportion of active-sites that Bortezomib inhibits. Our data indicate that Bortezomib achieves this severe inhibition by triggering secondary changes in proteasome structure that further inhibit proteasome activity. Comparing MM cells to other, Bortezomib-resistant, cancer cells shows that the degree of proteasome inhibition is the greatest in MM cells and only there leads to proteasome stress, providing an explanation for why Bortezomib is effective against MM but not other cancers.
AU  - Pitcher,DS
AU  - de,Mattos-Shipley K
AU  - Tzortzis,K
AU  - Auner,HW
AU  - Karadimitris,A
AU  - Kleijnen,MF
EP  - 648
PY  - 2015///
SP  - 642
TI  - Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure
T2  - EBioMedicine
UR  - http://hdl.handle.net/10044/1/23496
VL  - 2
ER  -
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