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Specific binding of MAR/SAR DNA-elements by mutant p53

B F Müller1, D Paulsen, W Deppert

  • 1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.

Oncogene
|May 2, 1996
PubMed
Summary

Mutant p53 proteins gain oncogenic properties by interacting with specific DNA elements. This novel interaction with nuclear matrix/scaffold attachment regions (MAR/SAR) may drive cancer progression.

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Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Single missense point mutations inactivate the tumor suppressor p53 in many human cancers.
  • Mutant p53 proteins can acquire dominant oncogenic 'gain of function' properties.
  • The molecular mechanisms underlying mutant p53's oncogenic functions remain largely unknown.

Purpose of the Study:

  • To identify novel biochemical activities of mutant p53.
  • To elucidate the molecular basis of mutant p53's oncogenic 'gain of function'.

Main Methods:

  • Biochemical assays to detect specific DNA-binding activities of mutant p53.
  • Characterization of the binding affinity and specificity for MAR/SAR DNA elements.
  • Mapping of the MAR/SAR-binding region within mutant p53.

Main Results:

  • Mutant p53 exhibits a specific, high-affinity interaction with MAR/SAR DNA elements.
  • This DNA-binding activity is distinct from previously identified p53 DNA-binding activities.
  • The MAR/SAR-binding region involves the mutated core and C-terminal domains of mutant p53.

Conclusions:

  • Mutant p53 possesses a novel biochemical activity involving MAR/SAR DNA elements.
  • This specific interaction may contribute to the oncogenic properties of mutant p53.
  • Interference with nuclear processes regulated by MAR/SAR elements could mediate pleiotropic oncogenic effects.

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