Yeda Research and Develpment & Co. Ltd

Mark Boldin

David Wallach

Igor Mett

Eugene Varfolomeev

Tanya Goncharov

Yury V Golstev

Andrei Kovalenko

Nikolai Malinin

Zeev Pancer

A DNA sequence encoding a protein capable of binding to a tumor necrosis factor receptor-associated factor (TRAF) molecule, TRAF-binding proteins, their isoforms, analogs, fragments and derivatives encoded by the DNA sequence, their methods for the production of the DNA sequences and proteins, and the uses for the DNA sequence and proteins.

Modulators of TNF receptor associated factor (TRAF), their preparation and use

The present invention provides proteins capable of modulating or mediating the FAS receptor ligand or TNF effect on cells carrying FAS receptor or p55 receptor by binding or interacting with MORT-1 protein, which in turn binds to the intracellular domain of the FAS receptor or to another protein TRADD which binds to the p55 receptor. In addition, peptide inhibitors that interfere with the proteolytic activity of MORT-1-binding proteins having proteolytic activity are provided, as well as a method of designing them.

Modulators of the function of FAS receptors and other proteins

Proteins capable of modulating the function of FAS/APO1 are provided. The proteins may be prepared by culturing a host cell transformed with a vector containing the DNA encoding such a protein under suitable conditions and isolating the protein.

Modulators of the function of FAS/APO1 receptors

The present invention generally concerns novel proteins which bind to the intracellular domains of the p55 and p75 TNF-Rs and the FAS-R, which are capable of modulating the function of the p55 and p75 TNF-Rs and the FAS-R, and the DNA sequences which encode them. The present invention also concerns new soluble oligomeric TNF-Rs, oligomeric FAS-Rs and oligomeric receptors having a mixture of TNF-Rs and FAS-Rs. In addition, the present invention concerns methods of preparation and uses of all of the aforementioned.

Modulator of TNF/NGF superfamily receptors and soluble oligomeric TNF/NGF superfamily receptors

Modulators of the function of FAS/AP01 receptors

A modulator of regulatory cellular events occurring intracellularly which are mediated by regulatory proteins containing a 'death domain' motif is provided. The 'death domain' is a regulatory portion of the regulatory proteins, and the modulator is capable of interacting with one or more &#x2018;death domain&#x2019; motifs contained in the regulatory proteins and affecting the regulatory action of one or more of the regulatory proteins. The modulator preferably is capable of interacting with &#x2018;death domain&#x2019; motifs within p55-TNF-R, FAS/APO1-R, NGF-R, MORT-1, RIP, TRADD, or ankyrin. A method for producing the modulators is also provided. The modulators are useful for modulating functions mediated in cells by proteins containing the &#x2018;death domain&#x2019;.

Modulators of regulatory proteins

The present invention provides proteins capable of modulating or mediating the FAS receptor ligand or TNF effect on cells carrying FAS receptor or p55 receptor by binding or interacting with MORT-1 protein, which in turn binds to the intracellular domain of the FAS receptor or to another protein TRADD which binds to the p55 receptor. In addition, peptide inhibitors which interfere with the proteolytic activity of MORT-1-biding proteins having proteolytic activity are provided as well as a method of designing them.

A modulator of regulatory cellular events occurring intracellularly which are mediated by regulatory proteins containing a &ldquo;death domain&rdquo; motif is provided. The &ldquo;death domain&rdquo; is a regulatory portion of the regulatory proteins, and the modulator is capable of interacting with one or more &ldquo;death domain&rdquo; motifs contained in the regulatory proteins and affecting the regulatory action of one or more of the regulatory proteins. The modulator preferably is capable of interating with &ldquo;death domain&rdquo; motifs within p55-TNF-R, FAS/APO1-R, NGF-R, MORT-1, RIP, TRADD, or ankryin, as illustrated in the Figure. A method for producing the modulators is also provided. The modulators are useful for modulating functions mediated in cells by proteins containing the &ldquo;death domain&rdquo;.

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Moscow, Russia

Mark Boldin