Selective induction of cell death by delivery of amino-terminal interleukin-1-α pro-piece polypeptide
AssigneeThe Regents of the University of California
InventorsAllan S. Pollock, David H. Lovett, Johanna Turck
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Abstract
The present invention is directed to compositions and methods for selective induction of apoptosis in cancer cells, particularly malignant cancer cells, by delivery of a IL-1α propiece polypeptide (e.g., a native IL-1α propiece polypeptide, including IL-1α propiece polypeptide variant) to a cancer cell.
Claims12
An isolated nucleic acid molecule encoding an apoptosis-inducing polypeptide comprising:
- a) an apoptosis-inducing domain comprising amino acid residues 75-108 of SEQ ID NO:2 or a biologically active variant thereof retaining apoptosis-inducing activity;
- and
- b) a nuclear localization sequence, wherein the nuclear localization sequence is obtained from a polypeptide other than a polypeptide of SEQ ID NO:2,
- wherein the nuclear localization sequence and apoptosis-inducing domain are operably joined.
An isolated nucleic acid molecule encoding an apoptosis-inducing polypeptide comprising:
- a) a nuclear localization sequences;
- and
- b) an apoptosis-inducing domain comprising amino acid residues 75-108 of SEQ ID NO:2 or a biologically active variant thereof retaining apoptosis-inducing activity;
- wherein the nuclear localization sequence and apoptosis-inducing domain are operably joined, and wherein the apoptosis-inducing polypeptide comprises an amino acid sequence other than SEQ ID NO:2.
An isolated nucleic acid molecule encoding an apoptosis-inducing polypeptide comprising an amino acid sequence selected from the group consisting of:
- a) amino acid residues 1-108 of SEQ ID NO:2;
- b) amino acid residues 11-118 of SEQ ID NO:2;
- c) amino acid residues 34-118 of SEQ ID NO:2;
- d) amino acid residues 55-118 of SEQ ID NO:2;
- e) amino acid residues 55-108 of SEQ ID NO:2;
- f) amino acid residues 75-108 of SEQ ID NO:2 operably joined to a nuclear localization sequence, wherein the nuclear localization sequence is obtained from a polypeptide other than a polypeptide of SEQ ID NO:2;
- g) amino acid residues 75-118 of SEQ ID NO:2 operably joined to a nuclear localization sequence, wherein the nuclear localization sequence is obtained from a polypeptide other than a polypeptide of SEQ ID NO:2;
- h) amino acid residues 1-118 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- i) amino acid residues 1-108 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- j) amino acid residues 55-108 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- and
- k) a biologically active variant of any of a) through j) retaining apoptosis-inducing activity;
- with the proviso that the polypeptide is not a full-length IL-1α propiece polypeptide.
An isolated nucleic acid molecule encoding a polypeptide comprising an amino acid sequence selected from the group consisting of:
- a) amino acid residues 1-108 of SEQ ID NO:2;
- b) amino acid residues 11-118 of SEQ ID NO:2;
- c) amino acid residues 34-118 of SEQ ID NO:2;
- d) amino acid residues 55-118 of SEQ ID NO:2;
- e) amino acid residues 55-108 of SEQ ID NO:2;
- f) amino acid residues 75-108 of SEQ ID NO:2 operably joined to a nuclear localization sequence;
- g) amino acid residues 75-118 of SEQ ID NO:2 operably joined to a nuclear localization sequence;
- h) amino acid residues 1-118 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- i) amino acid residues 1-108 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- j) amino acid residues 55-108 of SEQ ID NO:2 operably joined to a leucine zipper domain;
- and
- k) a biologically active variant of any of a) through j) retaining apoptosis-inducing activity;
- wherein serine at position 87 of SEQ ID NO:2 is substituted with an amino acid other than serine.
Dependencies are inferred from the claim text.