The Rel/NF-κB signal transduction pathway : introduction

Rel/NF- Kappa B transcription factors include a collection of proteins, conserved from Drosophila to humans. Among model organisms, these transcription factors are notably absent in yeast and C. elegans; in part, this may be because one of the primary roles of these factors is to control a variety of physiological aspects of immune and inflammatory responses. A pathway similar to the Rel/NF- Kappa B signaling pathway may also control certain defense responses in plants. The Rel/NF- Kappa B proteins are related through a highly conserved DNA-binding/dimerization domain called the Rel homology (RH) domain. However, they can be divided into two classes based on sequences C-terminal to the RH domain. Members of one class (p105, p100, and Drosophila Relish) have long C-terminal domains that contain multiple copies of ankyrin repeats, which act to inhibit these molecules. Members of this class become active, shorter DNA-binding proteins (p105 to p50, p100 to p52) by either limited proteolysis or arrested translation. As such, members of this first class are generally not activators of transcription, except when they form dimers with members of the second class of Rel/NF- Kappa B transcription factors. The second class includes c-Rel (and its homologue v-Rel), RelB, RelA (p65), Dorsal, and Dif. These Rel proteins contain C-terminal activation domains, which are often not conserved at the sequence level across species, even though they can activate transcription in a variety of species.