Modified p53 tetramerization domains having hydrophobic amino acid substitutions
AssigneeThe Wistar Institute of Anatomy and Biology
InventorsThanos D. Halazonetis, Elena S. Stavridi
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Abstract
Modified p53 tetramerization domains which do not hetero-oligomerize with native p53 tetramerization domains are described. These modified p53 tetramerization domains have one or more of the following substitutions in the region of residues 325 to 355 of human p53: Leu330 substituted with Phe; Met340 substituted with Phe; Ala347 substituted with Ile; Leu348 substituted with Met; Ala353 substituted with Leu; Gln354 substituted with Leu; Ala355 substituted with Asp. Also described are p53 proteins containing these modified p53 tetramerization domains linked to a p53 DNA binding domain. These proteins and the nucleic acid sequences encoding them, are useful in ameliorating conditions associated with inappropriate p53 function.
Claims11
A modified p53 protein comprising:
- (a) p53 DNA binding domain, said domain (a) having the sequence of amino acids 93-293 of SEQ ID NO:
- 3;
- said sequence having an optional single amino acid substitution at amino acid residue 248, 273, or 284 of SEQ ID NO:
- 3;
- and
- (b) a modified p53 tetramerization domain that does not hetero-oligomerize with a wild type p53 tetramerization domain, said domain (b) having the sequence of amino acids 325 to 355 of SEQ ID NO:
- 3, wherein the amino acid residue 340 is Met or Phe.
A composition comprising:
- (a) a modified p53 protein comprising:.
- (1) a p53 DNA binding domain, said domain (1) having the sequence of amino acids 93-293 of SEQ ID NO:
- 3, said sequence having an optional single amino acid substitution at amino acid residue 248, 273, or 284 of SEQ ID NO:
- 3;
- and
- (2) a modified p53 tetramerization domain that does not hetero-oligomerize with a wild type p53 tetramerization domain, said domain (2) having the sequence of amino acids 325 to 355 of SEQ ID NO:
- 3, wherein amino acid residue 340 is Met or Phe;
- and
- (b) a carrier.
Dependencies are inferred from the claim text.