Conserved transactivation domain shared by interferon regulatory factors and Smad morphogens

Interferon regulatory factors (IRFs) regulate the transcription of both interferon-inducible genes and interferons themselves. Along with the N-terminal, DNA-binding, winged-helix domain, most IRFs contain the C-terminal domains that are shown to be related to the C-terminal domains in the proteins of the Smad family that mediate transcription activation in the transforming growth factor response pathway. Comparison of the IRF-Smad alignment to the known three-dimensional structure of human tumor suppressor Smad4 suggests that a conserved loop, equivalent to Loop 3 in Smad 4, is a determinant of protein-protein interaction in IRFs.