Phospho-ΔNp63α/NF-Y protein complex transcriptionally regulates DDIT3 expression in squamous cell carcinoma cells upon cisplatin exposure

Phospho-ΔNp63α/NF-Y protein complex transcriptionally regulates DDIT3 expression in squamous cell carcinoma cells upon cisplatin exposure

Cisplatin remains the most important chemotherapeutic agent for patients with human head and neck cancer. However, tumor cells often develop resistance to cisplatin-induced apoptosis. We previously found that head and neck squamous cell carcinoma (HNSCC) cells exposed to cisplatin display a marked A...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Vol. 9; no. 2; pp. 328 - 338
Main Authors: Huang, Yiping, Chuang, Alice Y., Romano, Rose A., Liégeois, Nanette J., Sinha, Satrajit, Trink, Barry, Ratovitski, Edward A., Sidransky, David
Format: Journal Article
Language:English
Published: Taylor & Francis 15-01-2010
Subjects:
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cycle
Landes
Organogenesis
Proteins
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Summary:Cisplatin remains the most important chemotherapeutic agent for patients with human head and neck cancer. However, tumor cells often develop resistance to cisplatin-induced apoptosis. We previously found that head and neck squamous cell carcinoma (HNSCC) cells exposed to cisplatin display a marked ATM-induced phosphorylation of ΔNp63α. However, the mutated ΔNp63α-S385G failed to undergo phosphorylation by ATM kinase. We used HNSCC cell lines expressing the wild type ΔNp63α or mutated ΔNp63α-S385G to determine the effect of S385G mutation on the ΔNp63α transcriptional activity and protein-protein interactions. The S385G mutation in ΔNp63α dramatically abolished the up-regulation/down-regulation of downstream gene targets and the binding of ΔNp63α−S385G to certain promoters. In contrast to the non-phosphorylated ΔNp63α-S385G, the phospho-ΔNp63α forms protein-protein complexes with NF-YA transcription factor and regulates the transcription of DDIT3 gene implicated in the programmed cell death of HNSCC cells upon cisplatin exposure. We suggest that the transcriptional activation of ΔNp63α through its phosphorylation by ATM kinase in HNSCC cells exposed to cisplatin is a critical step in the subsequent sensitivity of certain human head and neck cancers to platinum therapy.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.9.2.10432