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IGKJRB1 (first given by Honjo's group because this protein was isolated due to its binding to the J kappa recombination signal). The RBP-J/Su(H) DNA-binding protein has been shown to be a transcription factor (alternative names: Drosophila Suppressor of Hairless [ Su(H)], RBP-Jk, KBF2, CBF1) which plays a key role in transcriptional regulation by targeting the intracytoplasmic domain of Notch receptors and EBNA-2 (Epstein-Barr virus nuclear antigen [2]). It is a member of the neurogenic gene family including Notch, Delta, Enhancer of split E(spl) and Hairless. RBP-J is a member of the CSL family of DNA binding factors which mediate either transcriptional repression or transcriptional activation. CSL protein play a central role in Notch signalling and in EBV-induced immortalization.

In the Tang et al paper, it is not specified if the functional gene is localized at 9p13-12 or 9q13 [OMIM 147183].

RBP-J/Su(H) is a 60 kDa DNA binding protein recognizing a consensus sequence (C/T) GTGGGAA although it has no typical DNA binding motif. The structure of the RBP-J protein is strongly conserved during evolution among nematode, fruit fly, mouse, and human.

EBNA-2 is essential for transformation of primary human B lymphocytes and acts as a transcriptional activator of latent viral as well as cellular genes by interacting with RBP-J/Su(H). Thus, RBP-J/Su(H) is essential to B-lymphocyte transformation by EBV.
RBP-J/Su(H) knockout mice die before 10.5 days of gestation and show severe developmental defects in somites and neural tube.
RBP-J/Su(H) is a sequence-specific DNA binding protein which plays a central role in signalling downstream of the Notch receptor by physically interacting with its intracellular region.

The Notch receptor consists of a large extracellular region with epidermal growth factor-like repeats and an intracellular region with cdc10/ankyrin repeats. The membrane-proximal region called the RAM domain of the intracellular region has been shown to interact directly with RBP-J/Su(H). Furthermore, the truncated Notch containing the total intracellular region can transactivate the promoter of HES-1, the mammalian homolog of Hairy and Enhancer of split, which has RBP-J/SU(H) binding sites. Since the truncated form of Notch has been shown to be involved in the development of T cell leukemias in mice and humans, RBP-J/SU(H) is presumably involved in transformation of both T and B lymphocytes.

Intracellular events occurring after interaction of Notch with its ligand(s) are not understood. Two models were proposed to explain the direct association berween the surface receptor Notch and the nuclear DNA binding protein RBP-J/SU(H):

In either case, the Notch and RBP-J/SU(H) signal transduction pathway takes the simplest and shortest route from the surface to the nucleus.

In mammals, there are at least four Notch family members that can interact with RBP-J/SU(H). In addition there are multiple ligands for the Notch receptor. A mouse RBP-J related gene named RBP-J is expressed exclusively in lung in contrast to the ubiquitously expressed RBP-J/SU(H) [1].

LIM protein KyoT2 negatively regulates transcription by association with the RBP-J/SU(H) DNA-binding protein [1].

RBP-J/SU(H) belongs to a family of highly conserved CSL proteins with homologs in Drosophila (Suppressor of Hairless [Su(H)]) and Caenorhabditis elegans (Lag-1). RBP-J functions in both transfection assays RBP-J/SU(H) binds to a unique corepressor, CBF1 interacting corepressor (CIR) [3]. CIR binds to histone deacetylase and to SAP30 and serves as a linker between RBP-J1 and the histone deacetylase complex, and in vitro transcription assays as a transcriptional repressor.

[1] Minoguchi, S. et al. Mol. Cell.Biol. 17, 2679-2687 (1997).
[2] Taniguchi, Y. et al. Mol. Cell. Biol. 18, 644-654 (1998).
[3] Hsieh, J. J. et al. Proc. Natl. Acad. Sci. USA 96, 23-28 (1999).