Sanofi-Aventis

Rhone-Poulenc Rorer Pharmaceuticals Inc.

Centelion Sas

George H Searfoss, Iii

Yuri D Ivashchenko

Kenneth Lyle Clark

Kun Guo

Marco Pagnoni

Michael C Jaye

Victoria J South

Christopher Cheadle

George A Ricca

Stephen M French

The present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF &#x3b1; signaling pathway. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as 'TRAF2 truncated' or 'TRAF2TR' and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as &#x201c;TRAF2 truncated-deleted&#x201d; or &#x201c;TRAF2TD&#x201d;. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF &#x3b1; signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF &#x3b1; binding.

Variants of TRAF2 which act as an inhibitor of TNF-alpha (TNF&#x3b1;) signaling pathway

The present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF &#x3b1; signaling path-way. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as 'TRAF2 truncated' or 'TRAF2TR' and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as &#x201c;TRAF2 truncated-deleted&#x201d; or &#x201c;TRAF2TD&#x201d;. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF &#x3b1; signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF &#x3b1; binding.

Variants of traf2 which act as an inhibitor of tnf-alpha (tnf&#x3b1;) signaling pathway

This invention provides a unique SH3 binding domain core motif of the sequence RPLPXXP and cDNA clones encoding proteins which interact with the SH3 domain of c-src, as well as the amino acid sequences which mediate this binding. Another embodiment of this invention is a method of identifying SH3-binding proteins and elucidating the sequences which mediate binding. This method may be used as an assay to select compounds which bind to this site and which inhibit or enhance the binding of the SH3 domain.

Expression cloning of c-src SH3-domain binding proteins

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Birdsboro, PA, United States of America

George H Searfoss, Iii