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HERO ID
8331746
Reference Type
Journal Article
Title
The genetic depletion or the triptolide inhibition of TFIIH in p53-deficient cells induces a JNK-dependent cell death in Drosophila
Author(s)
Villicaã±A, C; Cruz, G; Zurita, M
Year
2013
Is Peer Reviewed?
Yes
Journal
Journal of Cell Science
ISSN:
0021-9533
EISSN:
1477-9137
Volume
126
Issue
11
Page Numbers
2502-2515
Language
English
DOI
10.1242/jcs.122721
Abstract
Transcription factor IIH (TFIIH) participates in transcription, nucleotide excision repair and the control of the cell cycle. In the present study, we demonstrate that the Dmp52 subunit of TFIIH in Drosophila physically interacts with the fly p53 homologue, Dp53. The depletion of Dmp52 in the wing disc generates chromosome fragility, increases apoptosis and produces wings with a reduced number of cells; cellular proliferation, however, is not affected. Interestingly, instead of suppressing the apoptotic phenotype, the depletion of Dp53 in Dmp52-depleted wing disc cells increases apoptosis and the number of cells that suffer from chromosome fragility. The apoptosis induced by the depletion of Dmp52 alone is partially dependent on the JNK pathway. In contrast, the enhanced apoptosis caused by the simultaneous depletion of Dp53 and Dmp52 is absolutely JNK-dependent. In this study, we also show that the anti-proliferative drug triptolide, which inhibits the ATPase activity of the XPB subunit of TFIIH, phenocopies the JNK-dependent massive apoptotic phenotype of Dp53-depleted wing disc cells; this observation suggests that the mechanism by which triptolide induces apoptosis in p53-deficient cancer cells involves the activation of the JNK death pathway. ©2013. Published by The Company of Biologists Ltd.
Keywords
Apoptosis; Drosophila; JNK; P53; TFIIH; Triptolide
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