Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul;2(7):695-711.
doi: 10.1177/1947601911421925.

The c-Rel Transcription Factor in Development and Disease

Thomas D Gilmore  1 , Steve Gerondakis
Affiliations

The c-Rel Transcription Factor in Development and Disease

Thomas D Gilmore et al. Genes Cancer. 2011 Jul.

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.

PubMed Disclaimer

Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
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.
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.
See this image and copyright information in PMC

References

    1. Gilmore TD. Introduction to NF-κB: players, pathways, perspectives. Oncogene. 2006;25:6680-4 - PubMed
    1. Martin AG, Fresno M. Tumor necrosis factor-α activation of NF-κB requires the phosphorylation of Ser-471 in the transactivation domain of c-Rel. J Biol Chem. 2000;275:24383-91 - PubMed
    1. Martin AG, San-Antonio B, Fresno M. Regulation of nuclear factor κB transactivation: implication of phosphatidylinostitol 3-kinase and protein kinase C ζ in c-Rel activation by tumor necrosis factor α. J Biol Chem. 2001;276:15840-9 - PubMed
    1. Starczynowski DT, Reynolds JG, Gilmore TD. Deletion of either C-terminal transactivation subdomain enhances the in vitro transforming activity of human transcription factor REL in chicken spleen cells. Oncogene. 2003;22:6928-36 - PubMed
    1. Leeman JR, Weniger MA, Barth TF, Gilmore TD. Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL. Oncogene. 2008;27:6770-81 - PMC - PubMed

LinkOut - more resources