Imperial College London
Portrait Picture

ProfessorNicholasMazarakis

Faculty of Medicine, Department of Brain Sciences

Chair MolBioMedicine and Head of Gene Therapy
 
 
 
//

Contact

 

+44 (0)20 7594 7024n.mazarakis Website

 
 
//

Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
//

Location

 

E402Burlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pazarentzos:2014:10.15252/embj.201488183,
author = {Pazarentzos, E and Mahul-Mellier, A-L and Datler, C and Chaisaklert, W and Hwang, M-S and Kroon, J and Qize, D and Osborne, F and Al-Rubaish, A and Al-Ali, A and Mazarakis, ND and Aboagye, EO and Grimm, S},
doi = {10.15252/embj.201488183},
journal = {The EMBO Journal},
pages = {2814--2828},
title = {I kappa B alpha inhibits apoptosis at the outer mitochondrial membrane independently of NF-kappa B retention},
url = {http://dx.doi.org/10.15252/embj.201488183},
volume = {33},
year = {2014}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IκBα resides in the cytosol where it retains the inducible transcription factor NFκB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NFκB that accumulate high amounts of mitochondrial IκBα as a NFκB target gene. 3T3 IκBα−/− cells also become protected from apoptosis when IκBα is specifically reconstituted at the OMM. Using various IκBα mutants, we demonstrate that apoptosis inhibition and NFκB inhibition can be functionally and structurally separated. At mitochondria, IκBα stabilises the complex of VDAC1 and hexokinase II (HKII), thereby preventing Bax recruitment to VDAC1 and the release of cytochrome c for apoptosis induction. When IκBα is reduced in tumour cells with constitutively active NFκB, they show an enhanced response to anticancer treatment in an in vivo xenograft tumour model. Our results reveal the unexpected activity of IκBα in guarding the integrity of the OMM against apoptosis induction and open possibilities for more specific interference in tumours with deregulated NFκB.
AU  - Pazarentzos,E
AU  - Mahul-Mellier,A-L
AU  - Datler,C
AU  - Chaisaklert,W
AU  - Hwang,M-S
AU  - Kroon,J
AU  - Qize,D
AU  - Osborne,F
AU  - Al-Rubaish,A
AU  - Al-Ali,A
AU  - Mazarakis,ND
AU  - Aboagye,EO
AU  - Grimm,S
DO  - 10.15252/embj.201488183
EP  - 2828
PY  - 2014///
SN  - 0261-4189
SP  - 2814
TI  - I kappa B alpha inhibits apoptosis at the outer mitochondrial membrane independently of NF-kappa B retention
T2  - The EMBO Journal
UR  - http://dx.doi.org/10.15252/embj.201488183
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000345770000008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.embopress.org/doi/full/10.15252/embj.201488183
VL  - 33
ER  -
Download