Modulators of the functions of receptors of the tnf/ngf receptor family and other proteins

Abstract

Proteins which are capable of modulating/mediating the function of RIP, their preparation and uses are provided.

1 . A pharmaceutical composition for modulating the RIP effect on cells, comprising, as active ingredient, a recombinant animal virus vector encoding a protein capable of binding a cell surface receptor and encoding the RAP protein encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706. 
     
     
         2 . A method of modulating processes that are mediated/modulated by RIP directly or indirectly and which include the inhibition of NF-κB and JNK, comprising treating said cells with one or more polypeptides capable of binding to RIP, wherein said treating of cells comprises introducing into cells a DNA sequence encoding said one or more polypeptides in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, and said one or more polypeptides being selected from the group consisting of:
 (a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706;   (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and   (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.   
     
     
         3 . A method for the modulation or mediation of the RIP modulated/mediated intracellular effects on the inflammation, cell death or cell survival pathways in which RIP is involved directly, or indirectly via other modulators/mediators of these pathways, comprising treating cells with one or more polypeptides, wherein said treating of cells comprises introducing into said cells a DNA sequence encoding said polypeptide in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, and said one or more polypeptides being selected from the group consisting of:
 (a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706;   (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and   (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.   
     
     
         4 . A method according to  claim 3 , wherein said treating of said cells is by transfection of said cells with a recombinant animal virus vector comprising:
 (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein (ligand) that is capable of binding to a specific cell surface receptor on the surface of said cells to be treated and a second sequence encoding said polypeptide, that when expressed in said cells is capable of modulating/mediating the activity of RIP; and   (b) infecting said cells with said vector of (a).   
     
     
         5 . A method for treating tumor cells or HIV-infected cells or other diseased cells, comprising:
 (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein capable of binding to a specific tumor cell surface receptor or HIV-infected cell surface receptor or receptor carried by other diseased cells and a sequence encoding a polypeptide, that when expressed in said tumor, HIV-infected, or other diseased cell is capable of enhancing the RIP modulated/mediated direct or indirect killing of said cell, wherein said one or more polypeptides are selected from the group consisting of:   (a) a RIP-associated protein (RAP) encoded by a DNA sequence in a clone deposited with Collection Nationale de Cultures de Microorganismes under accession number I-2706;   (b) a fragment of (a) which is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP; and   (c) an analog of (a) or (b) which differs from the sequence of (a) or (b) by no more than 10 substitutions, deletions and/or insertions of amino acid residues and is capable of binding to RIP or inhibiting the NF-κB inducing effect of RIP.