Dual regulation of the DeltaNp63 transcriptional activity by DeltaNp63 in human nasopharyngeal carcinoma cell.
p63 splicing variants lacking NH(2)-terminal transactivating domain, known as DeltaNp63, are thought to antagonize p53 and p63 functions and are suggested to play roles in keratinocyte differentiation. Here, we show that DeltaNp63 has a dual-regulatory effect on the activity of its own promoter in NPC-076 cell. Down-regulation of the transcriptional activity is observed when DeltaNp63 is present in low levels. In contrast, up-regulation of DeltaNp63 transcriptional activity is observed when DeltaNp63 is expressed at higher levels. The down-regulation effect is abolished when the p53-binding site of the DeltaNp63 promoter is mutated. In sharp contrast, similar mutation does not affect the up-regulation of the DeltaNp63 transcriptional activity under the same experimental conditions. Further study shows that the up-regulation is correlated with the activation of the STAT3, as the blockade of STAT3 nuclear translocation abolishes the up-regulation by DeltaNp63. Thus, DeltaNp63 exerts a bidirectional regulation of the DeltaNp63 transcriptional activity in NPC-076 cell.
Chu
Wing-Keung
WK
Department of Physiology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Lee
Kuei-Ching
KC
Chow
Shu-Er
SE
Chen
Jan-Kan
JK
D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009303:Nasopharyngeal Neoplasms; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins