TRAF Interacting Protein With Forkhead Associated Domain A (TIFA)

The deduced mouse and human proteins contain 184 amino acids and have a central forkhead-associated (FHA) domain, which is a phosphopeptide-binding motif. overexpressed mouse Tifa bound both Traf6 and Irak1 and enhanced the interaction between Traf6 and Irak1. Substitution of glu178 with alanine in the TRAF6-binding domain of mouse Tifa abolished the interaction between Tifa and Traf6. In transient transfection assays, Tifa carrying this point mutation or Tifa carrying mutations in the FHA domain that abolished phosphopeptide binding failed to activate NFKB or JNK. Analysis of endogenous proteins in mouse pre-B cells and mouse embryonic fibroblasts indicated that Tifa associated constitutively with Traf6, whereas it associated with Irak1 in an Il1 stimulation-dependent manner.