p73beta, unlike p53, suppresses growth and induces apoptosis of human papillomavirus E6-expressing cancer cells.
Human papillomavirus (HPV) is the major cause of cervical cancer worldwide. HPV-E6 protein targets the p53 tumor suppressor protein for degradation by ubiquitin-mediated proteolysis making such cancers resistant to p53-gene therapy. Here we show that infection of human cancer cells by E6-expressing adenovirus (Ad-E6) leads to degradation of both wild-type or mutant p53 protein. Interestingly, the p53-homologue candidate tumor suppressor p73 is not degraded in Ad-E6 infected cancer cells. Wild-type p73beta and not wild-type p53 or mutant p73 is a potent inhibitor of cancer colony growth and inducer of apoptosis, despite HPV-E6 overexpression. The results suggest a novel strategy using p73beta in gene therapy of HPV-E6 expressing cancers.
Prabhu
N S
NS
Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
Somasundaram
K
K
Satyamoorthy
K
K
Herlyn
M
M
El-Deiry
W S
WS
D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008025:Ligases / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D011485:Protein Binding; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D008025:Ligases