Abstract: Disclosed is the isolation and characterization of EI24, a novel gene whose 2.4 kb mRNA is induced following etoposide treatment. Induction of EI24 mRNA by etoposide required expression of wild-type p53. Overexpression of functional p53 was sufficient to induce expression of the EI24 mRNA. The EI24 mRNA was also induced in a p53-dependent manner by ionizing irradiation of primary murine thymocytes. The invention is thus directed to an isolated EI24 protein, nucleotide sequences coding for and regulating expression of the protein, antibodies directed against the protein, and recombinant vectors and host cells containing the genetic sequences coding for and regulating the expression of the protein sequence. The invention is also directed to genomic DNA, cDNA, and RNA encoding the EI24 protein sequence and to corresponding antisense RNA sequences. Antibodies can be used to detect EI24 in biological specimens, including, for example, human tissue samples.

Abstract: Novel polypeptides having anti-apoptotic activity, and methods of screening for such novel polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides; Compounds that regulate or modulate apoptosis and/or anti-apoptotic activity, such as compounds having anti-apoptotic activity, and such as compounds that induce, restore, or modulate apoptosis and/or inhibit, diminish, or modulate anti-apoptotic activity, methods of screening for such compounds, and methods of using such compounds in the therapeutic treatment of diseases; Methods of treating eukaryotic cells with compounds that regulate or modulate apoptosis and/or anti-apoptotic activity; Methods of enhancing the stability, growth, and/or productivity of eukaryotic cells; Pharmaceutical compositions that regulate or modulate apoptosis and/or anti-apoptotic activity.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating apoptosis in cells, and to methods of modulating apoptosis employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to a novel peptide designated the “GD domain,” which is essential both to Bak's interaction with Bcl-xL, and to Bak's cell killing function. Methods of identifying agonists or antagonists of GD domain function are provided. The GD domain is responsible for mediating key protein/protein interactions of significance to the actions of multiple cell death regulatory molecules.

Abstract: Novel polypeptides having anti-apoptotic activity, and methods of screening for such novel polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides; Compounds that regulate or modulate apoptosis and/or anti-apoptotic activity, such as compounds having anti-apoptotic activity, and such as compounds that induce, restore, or modulate apoptosis and/or inhibit, diminish, or modulate anti-apoptotic activity, methods of screening for such compounds, and methods of using such compounds in the therapeutic treatment of diseases; Methods of treating eukaryotic cells with compounds that regulate or modulate apoptosis and/or anti-apoptotic activity; Methods of enhancing the stability, growth, and/or productivity of eukaryotic cells; Pharmaceutical compositions that regulate or modulate apoptosis and/or anti-apoptotic activity.

Abstract: Novel polypeptides having anti-apoptotic activity, and methods of screening for such novel polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides; Compounds that regulate or modulate apoptosis and/or anti-apoptotic activity, such as compounds having anti-apoptotic activity, and such as compounds that induce, restore, or modulate apoptosis and/or inhibit, diminish, or modulate anti-apoptotic activity, methods of screening for such compounds, and methods of using such compounds in the therapeutic treatment of diseases; Methods of treating eukaryotic cells with compounds that regulate or modulate apoptosis and/or anti-apoptotic activity; Methods of enhancing the stability, growth, and/or productivity of eukaryotic cells; Pharmaceutical compositions that regulate or modulate apoptosis and/or anti-apoptotic activity.

Abstract: Novel polypeptides having anti-apoptotic activity, and methods of screening for such novel polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides; Compounds that regulate or modulate apoptosis and/or anti-apoptotic activity, such as compounds having anti-apoptotic activity, and such as compounds that induce, restore, or modulate apoptosis and/or inhibit, diminish, or modulate anti-apoptotic activity, methods of screening for such compounds, and methods of using such compounds in the therapeutic treatment of diseases; Methods of treating eukaryotic cells with compounds that regulate or modulate apoptosis and/or anti-apoptotic activity; Methods of enhancing the stability, growth, and/or productivity of eukaryotic cells; Pharmaceutical compositions that regulate or modulate apoptosis and/or anti-apoptotic activity.

Abstract: Active Survival Domains in the Insulin-like Growth Factor-I Receptor (IGF-IR) required for transmitting the survival signal in vertebrate cells have been identified. In FL5.12 cells transfected with wild type IGF-I receptors, IGF-I provided protection from IL-3 withdrawal analogous to the protection afforded by expression of Bcl-2. Under the same conditions, IGF-I did not have a significant mitogenic effect on FL5.12 cells expressing IGF-I receptors. An IGF-I receptor with a mutation at the ATP-binding site did not provide protection from apoptosis. However, mutations at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) in the kinase domain resulted in receptors that retained survival function. In the C-terminus of the IGF-IR, mutation at tyrosine 1251 and at histidine 1293 and lysine 1294 abolished apoptotic function, whereas mutation of the four scrines at 1280-1283 did not affect survival. Surprisingly, receptors truncated at the C-terminus had enhanced anti-apoptotic function.

Abstract: Disclosed is the isolation and characterization of EI24, a novel gene whose 2.4 kb mRNA is induced following etoposide treatment. Induction of EI24 mRNA by etoposide required expression of wild-type p53. Overexpression of functional p53 was sufficient to induce expression of the EI24 mRNA. The EI24 mRNA was also induced in a p53-dependent manner by ionizing irradiation of primary murine thymocytes. The invention is thus directed to an isolated EI24 protein, nucleotide sequences coding for and regulating expression of the protein, antibodies directed against the protein, and recombinant vectors and host cells containing the genetic sequences coding for and regulating the expression of the protein sequence. The invention is also directed to genomic DNA, cDNA, and RNA encoding the EI24 protein sequence and to corresponding antisense RNA sequences. Antibodies can be used to detect EI24 in biological specimens, including, for example, human tissue samples.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating apoptosis in cells, and to methods of modulating apoptosis employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to a novel peptide designated the “GD domain”, which is essential both to Bak's interaction with Bcl-xL, and to Bak's cell killing function. Methods of identifying agonists or antagonists of GD domain function are provided. The GD domain is responsible for mediating key protein/protein interactions of significance to the actions of multiple cell death regulatory molecules.

Abstract: Disclosed are compositions and methods of screening for targets for antiviral chemotherapy having anti-apoptotic activity, and compositions and methods of screening for antiviral compounds that interfere with the anti-apoptotic activity of such targets. The targets comprise viral polypeptides having anti-apoptotic activity, and polynucleotides encoding such polypeptides. An example of such targets is a group of viral polypeptides of human cytomegalovirus (HCMV) having anti-apoptotic activity, such as pUL36, pUL37S, and pUL37L, and the polynucleotides encoding such polypeptides. The antiviral compounds comprise polypeptide, polynucleotide, DNA, RNA, amino acid, nucleic acid, and chemical compositions, including the chemically modified forms of such compositions, that interfere with the anti-apoptotic function of the target polypeptides and polynucleotides, leading to the induction of apoptosis and, consequently, the prevention or inhibition of replication.

Abstract: Active Survival Domains in the Insulin-like Growth Factor-I Receptor (IGF-IR) required for transmitting the survival signal in vertebrate cells have been identified. In FL5.12 cells transfected with wild type IGF-I receptors, IGF-I provided protection from IL-3 withdrawal analogous to the protection afforded by expression of Bcl-2. Under the same conditions, IGF-I did not have a significant mitogenic effect on FL5.12 cells expressing IGF-I receptors. An IGF-I receptor with a mutation at the ATP-binding site did not provide protection from apoptosis. However, mutations at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) in the kinase domain resulted in receptors that retained survival function. In the C-terminus of the IGF-IR, mutation at tyrosine 1251 and at histidine 1293 and lysine 1294 abolished apoptotic function, whereas mutation of the four serines at 1280-1283 did not affect survival. Surprisingly, receptors truncated at the C-terminus had enhanced anti-apoptotic function.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating apoptosis in cells, and to methods of modulating apoptosis employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to a novel peptide designated the "GD domain," which is essential both to Bak's interaction with Bcl-x.sub.L, and to Bak's cell killing function. Methods of identifying agonists or antagonists of GD domain function are provided. The GD domain is responsible for mediating key protein/protein interactions of significance to the actions of multiple cell death regulatory molecules.

Abstract: Disclosed is the isolation and characterization of EI24, a novel gene whose 2.4 kb mRNA is induced following etoposide treatment. Induction of EI24 mRNA by etoposide required expression of wild-type p53. Overexpression of functional p53 was sufficient to induce expression of the EI24 mRNA. The EI24 mRNA was also induced in a p53-dependent manner by ionizing irradiation of primary murine thymocytes. The invention is thus directed to an isolated EI24 protein, nucleotide sequences coding for and regulating expression of the protein, antibodies directed against the protein, and recombinant vectors and host cells containing the genetic sequences coding for and regulating the expression of the protein sequence. The invention is also directed to genomic DNA, cDNA, and RNA encoding the EI24 protein sequence and to corresponding antisense RNA sequences. Antibodies can be used to detect EI24 in biological specimens, including, for example, human tissue samples.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating apoptosis in cells, and to methods of modulating apoptosis employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to a novel peptide designated the "GD domain," which is essential both to Bak's interaction with Bcl-x.sub.L, and to Bak's cell killing function. Methods of identifying agonists or antagonists of GD domain function are provided. The GD domain is responsible for mediating key protein/protein interactions of significance to the actions of multiple cell death regulatory molecules.