Disease relevance of Rbpj

• Here we report that conditionally disrupting the mouse RBP-J gene in a mosaic pattern to avoid embryonic lethality of RBP-J-deficiency caused hair loss, epidermal hyperkeratinization, and epidermal cyst formation [1].
• In the course of these studies, it was observed that coinjection of P-CRTs with large numbers of normal CBF1 thymocytes (F1 NTs) significantly reduced the GVHR of the P-CRTs as measured in Simonsen splenomegaly and [3H]TdR splenic proliferation assays [2].
• In addition, two candidate binding sites for the cellular transcription factor RBP-Jkappa/CBF1 were also identified in one of the Rta-responsive regions, which may play a role in mediating Rta transactivation similar to that observed in some KSHV Rta-responsive genes [3].
• We have raised monoclonal antibodies against the RBP-J kappa fusion protein which was synthesized in E. coli and unable to bind J kappa-RS [4].
• At 5 wk after the intraperitoneal infection of murine cytomegalovirus (MCMV) in adult (C3H/He x BALB/c) F1 (CBF1) mice, MCMV-DNA was noted mainly in the salivary glands (SG) [5].

Psychiatry related information on Rbpj

• We also show that null heterozygous mutations in the downstream cofactor RBP-J result in similarly specific spatial learning and memory deficits [6].

High impact information on Rbpj

• We also describe vascular defects in embryos homozygous for a mutation in the Rbpsuh gene, which encodes the primary transcriptional mediator of Notch signaling [7].
• Analysis of the enhancer regulating node-specific Nodal expression revealed the presence of binding sites for the RBP-J protein, the primary transcriptional mediator of Notch signaling [8].
• Our data demonstrated that Notch/RBP-J signaling regulates gammadelta T cell generation and migration, alphabeta T cell maturation, terminal differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells [9].
• We found that Msx2-interacting nuclear target protein (MINT) competed with the intracellular region of Notch for binding to a DNA binding protein RBP-J and suppressed the transactivation activity of Notch signaling [10].
• In addition, in mice with RBP-J-deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin [11].

Chemical compound and disease context of Rbpj

• The effect of fexofenadine on systemic anaphylaxis caused by IgE and anti-IgE was also examined in CBF1 mice injected with serum from NC/Nga mice with high IgE levels [12].

Biological context of Rbpj

• Assignment of the mouse Rbpsuh gene to chromosome 5 and one processed pseudogene Rbpsuh-rs3 to chromosome 6 [13].
• To explore the function of the RBP-J kappa gene in mouse embryogenesis, a mutation was introduced into the functional RBP-J kappa gene in embryonic stem (ES) cells by homologous recombination [14].
• The Notch intracellular region (RAMIC) interacts with a DNA binding protein RBP-J to activate transcription of genes that inhibit cell differentiation [15].
• To investigate the function of Notch-RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis [11].
• Here, we investigate the function of RBP-J in the development of mesodermal cell lineages by using the OP9 stroma coculture system [16].

Anatomical context of Rbpj

• To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated [17].
• We showed that inhibition of Notch/RBP-J signaling, by either conditional disruption of the Rbpsuh gene or treatment with a gamma-secretase inhibitor, could give rise to ectopic hair cells in the supporting cell region in organs of Corti from neonatal mouse cochleas where hair cells have not been considered to regenerate after birth [18].
• The RBP-J kappa gene is highly conserved in a wide variety of species and the Drosophila homologue has been shown to be identical to Suppressor of Hairless [Su(H)] which plays important roles in the development of the peripheral nervous system [14].
• Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas [18].
• The loss of RBP-J at an earlier developmental stage resulted in enhanced generation and accelerated emigration of gammadelta T cells, whereas alphabeta T cell development was arrested at the double-negative 3 stage [9].

Associations of Rbpj with chemical compounds

• Lymphoid progenitors deficient in RBP-J differentiate into B but not T cells when cultured in 2'-deoxyguanosine-treated fetal thymic lobes by hanging-drop fetal thymus organ culture [19].
• Class-specific plaque-forming cell (PFC) (gammaM, gamma1, gamma2, and gammaA) responses to type III pneumococcal polysaccharide (SSS-III) were studied in BALB/c x C57BL/6F1 (CBF1) mice with and without induction of an allogeneic effect [20].
• Metabolism of choline in brain of the aged CBF-1 mouse [21].
• In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices [21].
• Therefore, quantitative morphometry of nerve terminals stained with zinc iodide-osmium was carried out in soleus and extensor digitorum longus (EDL) muscles of CBF-1 mice at various ages from 5 to 32 months [22].

Physical interactions of Rbpj

• As development proceeds, RBPJL gradually replaces RBPJ in the PTF1 complex bound to Rbpjl and appears on the binding sites for the complex in the promoters of other acinar-specific genes, including those for the secretory digestive enzymes [23].
• We show that a mutant form of Ptf1a without the ability to bind Rbpj, while retaining its ability to interact with E-protein, is incapable of inducing GABAergic (Pax2)- and suppressing glutamatergic (Tlx3)-expressing cells in the chick and mouse neural tube [24].

Regulatory relationships of Rbpj

• Nrarp overexpression is able to block Notch-induced activation of CBF-1 [25].
• In addition, both ligands transmitted signal through the CBF-1-dependent pathway and stimulated the expression of HES-1, a direct target of Notch pathway [26].

Other interactions of Rbpj

• Taken together, mouse Notch1 RAMIC can experimentally be separated into three functional domains: the RAM domain and ANK repeats for RBP-J binding and co-repressor displacement and the C-terminal TAD [15].
• Loss of RBP-J and Pofut1 led to an accumulation of basal cell clusters characterized by the presence of cytokeratins (K5) and K14 and smooth muscle actin (SMA) during pregnancy [27].
• The transcription factor recombination signal sequence-binding protein Jkappa (RBP-J) is a key downstream element in the signaling pathway of all four mammalian Notch receptors that are critically involved in the control of embryonic and adult development [16].
• We have isolated a cDNA clone (RBP-2) for the protein (RBP-J kappa) which binds to immunoglobulin recombination signals with 23-base pair spacers (Matsunami, N., Hamaguchi, Y., Yamamoto, Y., Kuze, K., Kangawa, K., Matsuo, H., Kawaichi, M., and Honjo, T. (1989) Nature 342, 934-937) [28].
• The DNA binding activity was not affected by amino acid replacements within the integrase motif of the RBP-J kappa protein (230His-269His) [29].

Analytical, diagnostic and therapeutic context of Rbpj

• Site-directed mutagenesis study on DNA binding regions of the mouse homologue of Suppressor of Hairless, RBP-J kappa [29].
• Several lines of evidence indicated that partial denervation was rare in old CBF-1 mice, and therefore could not account for the findings above [30].
• We have investigated whether J kappa recombination signal sequence (RS) binding protein (RBP-J kappa) has any partial catalytic activities involved in the VDJ recombination reaction, such as cleavage, ligation, and bending of DNA [4].

References