The c-Rel Transcription Factor in Development and Disease

Abstract

c-Rel is a member of the nuclear factor κB (NF-κB) transcription factor family. Unlike other NF-κB proteins that are expressed in a variety of cell types, high levels of c-Rel expression are found primarily in B and T cells, with many c-Rel target genes involved in lymphoid cell growth and survival. In addition to c-Rel playing a major role in mammalian B and T cell function, the human c-rel gene (REL) is a susceptibility locus for certain autoimmune diseases such as arthritis, psoriasis, and celiac disease. The REL locus is also frequently altered (amplified, mutated, rearranged), and expression of REL is increased in a variety of B and T cell malignancies and, to a lesser extent, in other cancer types. Thus, agents that modulate REL activity may have therapeutic benefits for certain human cancers and chronic inflammatory diseases.

Keywords: B cells; NF-κB; REL; T cells; arthritis; c-Rel; cancer; signal transduction.

Figure 1.

Generalized structure of the human REL protein. The numbers below the figure indicate the limits of each domain. RHD = Rel homology domain; NLS = nuclear localization signal; RID = REL inhibitory domain; TAD1 = transactivation domain 1; TAD2 = transactivation domain 2. The red box indicates the approximate position of residues 308-330, encoded by exon 9, that are deleted in an alternatively spliced form of REL, which is overrepresented in many B lymphoma cell lines.

Figure 2.

c-Rel in normal development and disease. Shown are the major normal biological processes (green boxes) and pathologies (red boxes) in which c-Rel plays a role in T cells, B cells, and other cell types.