Structural highlights
Function
[REL_CHICK] Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family transcription factor that plays a critical role in lymphoid cell development and mediates CD28-induced expression of interleukin 2 (IL-2). The CD28 response element (CD28RE) in the IL-2 enhancer is nonameric and similar to the kappaB DNA target sites recognized by p65 homodimers. RESULTS: We have determined and refined the X-ray crystal structure of the c-Rel homodimer complexed to the CD28RE DNA site, 5'-AGAAATTCC-3', to 2.85 A resolution. The c-Rel homodimer binds CD28RE in a mode similar to that observed in the p65/IL-8 kappaB crystallographic complex. Binding studies reveal that the c-Rel homodimer recognizes the CD28RE with higher affinity as compared to other canonical kappaB sequences despite the nonconsensus A:T base pair at the 5' end of the CD28RE. Preferential recognition of the CD28RE by c-Rel results from the direct contacts between the protein and the DNA as well as intrasubunit interactions between the beta(f)-beta(g) loop in the dimerization domain and the DNA-contacting loop L1 of the N-terminal domain. Not only do these loops have different conformations in other Rel/DNA crystallographic complexes, but they also contain two of the five oncogenic point mutations found in v-Rel. CONCLUSIONS: The current structure indicates that a non-DNA-contacting loop in the dimerization domain and the DNA-contacting loop L1 may play critical roles in defining affinity and specificity. Two amino acid changes in these segments may account for the differential DNA binding by v-Rel as compared to that of c-Rel.
X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2.,Huang DB, Chen YQ, Ruetsche M, Phelps CB, Ghosh G Structure. 2001 Aug;9(8):669-78. PMID:11587641[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang DB, Chen YQ, Ruetsche M, Phelps CB, Ghosh G. X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2. Structure. 2001 Aug;9(8):669-78. PMID:11587641
