High throughput testing of the SV40 Large T antigen binding to cellular p53 identifies putative drugs for the treatment of SV40-related cancers.
SV40 has been linked to some human malignancies, and the evidence that this virus plays a causative role in mesothelioma and brain tumors is mounting. The major SV40 oncoprotein is the Large tumor antigen (Tag). A key Tag transforming activity is connected to its capability to bind and inactivate cellular p53. In this study we developed an effective, high throughput, ELISA-based method to study Tag-p53 interaction in vitro. This assay allowed us to screen a chemical library and to identify a chemical inhibitor of the Tag binding to p53. We propose that our in vitro assay is a useful method to identify molecules that may be used as therapeutic agents for the treatment of SV40-related human cancers.
Loyola University Medical Center, Cardinal Bernardin Cancer Center, Department of Pathology, Maywood, IL 60153, USA.
Michele
M
Carbone
Jennifer
J
Rudzinski
Maurizio
M
Bocchetta
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D027601:Polyomavirus Infections / Q000188:drug therapy*; D013539:Simian virus 40 / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000188:drug therapy*
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53