Modified p53 constructs which enhance DNA binding
AssigneeThe Wistar Institute of Anatomy and Biology
InventorThanos D. Halazonetis
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Abstract
A modified p53 protein or peptide having DNA binding in which amino acid residue 284 of a p53 protein or protein fragment is changed to Arginine or Lysine, is described. Also described are nucleotide sequences encoding the modified protein and vectors capable of expressing it.
Claims18
A modified p53 protein construct having DNA binding ability comprising a p53 sequence selected from the group consisting of:
- (a) a sequence that differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2 by the substitution of threonine at position 284 by arginine;
- and
- (b) a sequence that differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2 by the substitution of threonine at position 284 by arginine and by the substitution addition, or deletion of up to 20 amino acids.
A method of enhancing the DNA-binding ability of a p53 protein construct comprising the steps of:
- (a) providing a nucleic acid sequence encoding a p53 protein construct comprising a p53 sequence selected from the group consisting of:
- (i) at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2;
- and
- (ii) a sequence which differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2 by the substitution, addition or deletion of up to 20 amino acids;
- and
- (b) modifying the codon encoding threonine residue 284 to a codon encoding arginine, whereby the resulting modified p53 protein construct is characterized by enhanced DNA-binding ability.
A modified p53 protein construct having DNA binding ability comprising a p53 sequence selected from the group consisting of:
- (a) a sequence that differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2 by the substitution of threonine at position 284 of by lysine;
- and
- (b) a sequence that differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEO ID NO:2 by the substitution of threonine at position 284 by lysine and by the substitution addition, or deletion of up to 20 amino acids.
A method of enhancing the DNA-binding ability of a p53 protein construct, comprising the steps of:
- (a) providing a nucleic acid sequence encoding a p53 protein construct comprising a p53 sequence selected from the group consisting of:
- (i) at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID:2;
- and
- (ii) a sequence which differs from at least about amino acid 90 to about amino acid 290 of the sequence of SEQ ID NO:2 by the substitution, addition or deletion of up to 20 amino acids;
- and
- (b) modifying the codon encoding threonine residue 284 to a codon encoding lysine, whereby the resulting modified p53 construct is characterized by enhanced DNA-binding ability.
A modified p53 protein construct having DNA binding ability comprising full-length human wild-type p53 protein, SEQ ID NO:2, wherein the threonine at position 284 of the human p53 protein is changed to arginine.
Dependencies are inferred from the claim text.