Abstract |
Cisplatin was shown to induce the ataxia telangiectasia mutated (ATM)-dependent phosphorylation of tumor protein p63 isoform, (ΔNp63α), leading to a transcriptional regulation of specific genes implicated in the control of cell death of squamous cell carcinoma (SCC) cells. We previously observed that the cisplatin-induced phosphorylated (p)-ΔNp63α transcriptionally regulates the expression of specific microRNAs ( miRNAs) in SCC cells. We found here that cisplatin exposure of SCC cells led to modulation of the members of the autophagic pathway, such as Atg1/Ulk1, Atg3, Atg4A, Atg5, Atg6/Becn1, Atg7, Atg9A and Atg10, by a direct p-ΔNp63α-dependent transcriptional regulation. We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-ΔNp63α, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. Our data support the notion that the cisplatin-induced p-ΔNp63α could regulate key pathways implicated in response of cancer cells to chemotherapeutics.
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Authors | Yiping Huang, Rafael Guerrero-Preston, Edward A Ratovitski |
Journal | Cell cycle (Georgetown, Tex.)
(Cell Cycle)
Vol. 11
Issue 6
Pg. 1247-59
(Mar 15 2012)
ISSN: 1551-4005 [Electronic] United States |
PMID | 22356768
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATG5 protein, human
- Autophagy-Related Protein 5
- Cell Cycle Proteins
- Culture Media
- MicroRNAs
- Microtubule-Associated Proteins
- Phosphoproteins
- Protein Isoforms
- TP53 protein, human
- TP63 protein, human
- Trans-Activators
- Transcription Factors
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
- UVRAG protein, human
- Cisplatin
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Topics |
- Autophagy
- Autophagy-Related Protein 5
- Carcinoma, Squamous Cell
(metabolism, pathology)
- Cell Cycle Checkpoints
- Cell Cycle Proteins
(genetics, metabolism)
- Cell Line, Tumor
- Cell Survival
- Chromatin Immunoprecipitation
- Cisplatin
(pharmacology)
- Culture Media
(metabolism)
- Gene Expression Regulation, Neoplastic
- Humans
- MicroRNAs
(genetics, metabolism)
- Microtubule-Associated Proteins
(genetics, metabolism)
- Phosphoproteins
(genetics, metabolism)
- Protein Isoforms
(genetics, metabolism)
- RNA Processing, Post-Transcriptional
- Signal Transduction
- Trans-Activators
(genetics, metabolism)
- Transcription Factors
(genetics, metabolism)
- Transcription, Genetic
- Tumor Suppressor Protein p53
(genetics, metabolism)
- Tumor Suppressor Proteins
(genetics, metabolism)
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