Restore Wild-Type Functions to P53 Mutants Using an RNA- Based Combinatorial Approach

Abstract

The tumor suppressor p53 plays pivotal roles in maintaining the integrity of the genome and regulates cell cycle arrest and programmed cell death (apoptosis). Tumors without a functioning p53 are more likely to have a very aggressive clinical course. We proposed to use an RNA-based combinatorial approach to select for single-stranded RNA molecules that will bind to a mutant p53 protein, correct its conformation, and restore its sequence-specific DNA-binding activity. We have successfully accomplished the tasks we proposed for the first year of funding, including (1) expression and purification of human wild-type p53 protein in insect cells, (2) in vitro selection of RNA aptamers from a pool of RNA molecules that bind to p53 protein, and (3) sequence-specific DNA binding assays using the EMSA technique. Sequence and structural analysis of the selected RNAs revealed that the ability of RNA molecules to interfere with sequence-specific DNA binding of p53 may depend on their tertiary structures.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1998
Accession Number
ADA353779

Entities

People

  • Xiaoying Chen

Organizations

  • SRI International

Tags

DTIC Thesaurus Topics

  • Biomedical And Dental Materials
  • Breast Cancer
  • Cell Physiological Processes
  • Chemical Synthesis
  • Chemistry
  • Deoxyribonucleic Acids
  • Genetic Structures
  • Laboratory Animals
  • Materials
  • Molecules
  • Neoplasms
  • Nucleic Acids
  • Polymeric Films
  • Programmed Cell Death
  • Proteins
  • Recombinant Dna
  • Sequences

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics