Transcriptional activity of TAp63 promoter is regulated by c-jun.
The transcription factor p63 belongs to the p53 protein family and plays an important role in epithelial development. Recent studies showed that p63 is over-expressed in some human squamous cell carcinomas of the head and neck, suggesting a role in carcinogenesis. The p63 gene contains two promoters and alternative promoter usage generates two groups of proteins with (TAp63) or without (ΔNp63) the transactivation domain. Although the roles of TAp63 in epithelial development have been described in numerous recent studies, the regulation of its expression has not been elucidated. In this study, we showed that the transcriptional activity of the TAp63 promoter and TAp63 protein level were both up-regulated by an increased c-jun activity in Hep3B human hepatocellular carcinoma cell. Moreover, the elevated TAp63 expression was coincided with an increased binding of c-jun to the TAp63 promoter. Point mutation of the sp1 binding site within the TAp63 promoter region attenuated the effect of c-jun on TAp63 expression. Knockdown of TAp63 expression by shRNA led to increased proliferation of Hep3B cell compared to that of the mock cell, suggesting a growth suppressive effect of TAp63.
Yao
Jeng-Yuan
JY
Department of Physiology, College of medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Pao
Chia-Chu
CC
Chen
Jan-Kan
JK
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin; D020928:Mitogen-Activated Protein Kinases