Phosphorylated TP63 Induces Transcription of RPN13, Leading to NOS2 Protein Degradation
Copyright policy )Phosphorylated TP63 Induces Transcription of RPN13, Leading to NOS2 Protein Degradation
Head and neck squamous cell carcinoma cells exposed to cisplatin display ATM-dependent phosphorylation of the most predominant TP63 isoform (ΔNp63α), leading to its activation as a transcription factor. Here, we found that the phospho-ΔNp63α protein binds to the genomic promoter of RPN13 through the TP63-responsive element. We further found that the phospho-ΔNp63α protein associates with other transcription factors (DDIT3 (also known as CHOP), NF-Y, and NF-κB), activating RPN13 gene transcription. Furthermore, cisplatin-induced and phospho-ΔNp63α-dependent RPN13 gene transcription leads to NOS2 degradation. Finally, we show that RPN13 knockdown by siRNA essentially rescues NOS2 from cisplatin-dependent inactivation. These data provide a novel mechanism for the phospho-ΔNp63α-dependent regulation of NOS2 function in cells upon cisplatin treatment, contributing to the cell death pathway of tumor cells.
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
Membrane Glycoproteins, Base Sequence, Tumor Suppressor Proteins, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Nitric Oxide Synthase Type II, Antineoplastic Agents, Gene Expression Regulation, Neoplastic, CCAAT-Binding Factor, Cell Line, Tumor, Sequence Homology, Nucleic Acid, Trans-Activators, Humans, Cisplatin, Phosphorylation, RNA, Small Interfering, Promoter Regions, Genetic, Transcription Factor CHOP, Transcription Factors
Membrane Glycoproteins, Base Sequence, Tumor Suppressor Proteins, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Nitric Oxide Synthase Type II, Antineoplastic Agents, Gene Expression Regulation, Neoplastic, CCAAT-Binding Factor, Cell Line, Tumor, Sequence Homology, Nucleic Acid, Trans-Activators, Humans, Cisplatin, Phosphorylation, RNA, Small Interfering, Promoter Regions, Genetic, Transcription Factor CHOP, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).7 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!