Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication

J Bargonetti ¹, P N Friedman , S E Kern

⁰Department of Biological Sciences, Columbia University, New York, New York 10027.

Cell +

|

June 14, 1991

View abstract on PubMed

Summary

Normal p53 proteins bind to specific DNA sequences, but tumor-associated mutant p53 proteins do not. Viral proteins can interfere with this binding, impacting viral replication and cell division control.

Area Of Science

Molecular Biology
Virology
Oncology

Background

Mutations in the p53 tumor suppressor gene are common in human cancers.
The p53 protein plays a critical role in maintaining genomic stability and regulating cell division.

Purpose Of The Study

To investigate the DNA-binding capabilities of wild-type and mutant p53 proteins.
To explore the interaction between p53 and Simian Virus 40 (SV40) DNA.
To understand how viral proteins might influence p53's function.

Main Methods

Purification of wild-type and mutant p53 proteins using baculovirus expression vectors.
DNAase I footprinting assays to assess sequence-specific DNA binding.
Examination of p53 interactions with SV40 DNA in the presence of SV40 T antigen.

Main Results

Wild-type p53 proteins (human and murine) specifically bind to DNA sequences near the SV40 replication origin.
Mutant p53 proteins, frequently found in tumors, do not exhibit this specific DNA binding.
SV40 T antigen inhibits the binding of wild-type p53 to the viral DNA.

Conclusions

Normal p53 protein demonstrates sequence-specific DNA-binding activity, suggesting a role in regulating gene expression.
Oncogenic p53 mutations abolish this specific DNA-binding function.
Viral proteins can interfere with p53-DNA interactions, potentially modulating viral replication and cellular processes.

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