Imperial College London
Alternate

DrConcettaBubici

Faculty of Medicine, Faculty of Medicine Centre

Honorary Clinical Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 8432c.bubici

 
 
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Location

 

10.N6Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pham:2007,
author = {Pham, CG and Bubici, C and Zazzeroni, F and Knabb, JR and Papa, S and Kuntzen, C and Franzoso, G},
journal = {Mol Cell Biol},
pages = {3920--3935},
title = {Upregulation of Twist-1 by NF-kB blocks cytotoxicity induced by chemotherapeutic drugs},
volume = {27},
year = {2007}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - NF-B/Rel transcription factors are central to controlling programmed cell death (PCD). Activation of NF-B blocks PCD induced by numerous triggers, including ligand engagement of tumor necrosis factor receptor (TNF-R) family receptors. The protective activity of NF-B is also crucial for oncogenesis and cancer chemoresistance. Downstream of TNF-Rs, this activity of NF-B has been linked to the suppression of reactive oxygen species and the c-Jun-N-terminal-kinase (JNK) cascade. The mechanism by which NF-B inhibits PCD triggered by chemotherapeutic drugs, however, remains poorly understood. To understand this mechanism, we sought to identify unrecognized protective genes that are regulated by NF-B. Using an unbiased screen, we identified the basic-helix-loop-helix factor Twist-1 as a new mediator of the protective function of NF-B. Twist-1 is an evolutionarily conserved target of NF-B, blocks PCD induced by chemotherapeutic drugs and TNF- in NF-B-deficient cells, and is essential to counter this PCD in cancer cells. The protective activity of Twist-1 seemingly halts PCD independently of interference with cytotoxic JNK, p53, and p19ARF signaling, suggesting that it mediates a novel protective mechanism activated by NF-B. Indeed, our data indicate that this activity involves a control of inhibitory Bcl-2 phosphorylation. The data also suggest that Twist-1 and -2 play an important role in NF-B-dependent chemoresistance.
AU  - Pham,CG
AU  - Bubici,C
AU  - Zazzeroni,F
AU  - Knabb,JR
AU  - Papa,S
AU  - Kuntzen,C
AU  - Franzoso,G
EP  - 3935
PY  - 2007///
SP  - 3920
TI  - Upregulation of Twist-1 by NF-kB blocks cytotoxicity induced by chemotherapeutic drugs
T2  - Mol Cell Biol
VL  - 27
ER  -
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