DNA-binding activity of wild-type p53 protein is mediated by the central part of the molecule and controlled by its C terminus

R. Wolkowicz, A. Peled, N. Elkind, V. Rotter

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The DNA binding activity of wild type p53 is central to its activity. The 'central' part of the molecule, where most mutations appear in primary human tumors, is the actual DNA binding domain. The C-terminal part was shown to exert a negative effect on the DNA binding activity. In the present study we show that while anti-p53 antibodies recognizing the C terminus of the wild type p53 facilitate DNA binding activity, blocking of the wild type specific epitope by specific anti-p53 antibodies, inhibited the DNA binding activity of the wild type p53 protein. An alternatively spliced p53 protein exhibits an augmented DNA binding activity. The fact that most p53 mutants have lost the wild type p53 conformation specific epitope, coupled with the observation that blocking of this site by binding specific antibodies, prevents the interaction of wild type p53 with DNA, suggests that maintaining the correct structural conformation of this site is central for DNA binding activity. Still, the internal structure of the p53 target and particularly the length of the sequence between the two tandem inverted repeats, is critical for protein-DNA interaction behavior.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalCancer Detection and Prevention
Volume22
Issue number1
Publication statusPublished - 1998

Fingerprint

DNA
Proteins
Epitopes
Anti-Idiotypic Antibodies
Inverted Repeat Sequences
Antibody Binding Sites
Mutation
Neoplasms

Keywords

  • DNA binding
  • Functional domains
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DNA-binding activity of wild-type p53 protein is mediated by the central part of the molecule and controlled by its C terminus. / Wolkowicz, R.; Peled, A.; Elkind, N.; Rotter, V.

In: Cancer Detection and Prevention, Vol. 22, No. 1, 1998, p. 1-13.

Research output: Contribution to journalArticle

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