Genomes and Genes
Gene Symbol: Rbpj
Description: recombination signal binding protein for immunoglobulin kappa J region
Alias: AI843960, CBF1, Igkjrb, Igkrsbp, RBP-J, RBP-J kappa, RBP-Jkappa, RBPjk, Rbpsuh, recombining binding protein suppressor of hairless, J-kappa recombination signal binding protein, Jkappa recombination signal binding protein
- Oka C, Nakano T, Wakeham A, de la Pompa J, Mori C, Sakai T, et al. Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development. 1995;121:3291-301 pubmed..Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-J kappa gene was revealed to be essential for postimplantation development of mice. ..
- Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R. Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci. 2010;30:3489-98 pubmed publisher..for Notch signaling in the telencephalon by generating tamoxifen-inducible conditional knock-out mice that lack Rbpj, an intracellular signal mediator of all Notch receptors...
- Huppert S, Ilagan M, De Strooper B, Kopan R. Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation. Dev Cell. 2005;8:677-88 pubmed..These data clarify multiple roles for Notch signaling during segmentation and suggest that the earliest stages of somitogenesis are regulated by both Notch-dependent and Notch-independent functions of presenilin. ..
- Shimizu T, Kagawa T, Inoue T, Nonaka A, Takada S, Aburatani H, et al. Stabilized beta-catenin functions through TCF/LEF proteins and the Notch/RBP-Jkappa complex to promote proliferation and suppress differentiation of neural precursor cells. Mol Cell Biol. 2008;28:7427-41 pubmed publisher..Thus, the GSK3beta/beta-catenin signaling axis regulated by FGF and Wnt signals plays a pivotal role in the maintenance of neural stem/precursor cells by linking the cell proliferation to the inhibition of differentiation. ..
- Hori K, Cholewa Waclaw J, Nakada Y, Glasgow S, Masui T, Henke R, et al. A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling. Genes Dev. 2008;22:166-78 pubmed publisher..The transcription factor Rbpj is a transducer of the Notch signaling pathway that functions to maintain neural progenitor cells...
- Minter L, Turley D, Das P, Shin H, Joshi I, Lawlor R, et al. Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21. Nat Immunol. 2005;6:680-8 pubmed..Thus, using gamma-secretase inhibitors to modulate Notch signaling may prove beneficial in treating TH1-mediated autoimmunity. ..
- Tanigaki K, Tsuji M, Yamamoto N, Han H, Tsukada J, Inoue H, et al. Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity. 2004;20:611-22 pubmed..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. ..
- Castel D, Mourikis P, Bartels S, Brinkman A, Tajbakhsh S, Stunnenberg H. Dynamic binding of RBPJ is determined by Notch signaling status. Genes Dev. 2013;27:1059-71 pubmed publisher..The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and, together with the transcription factor moiety of Notch (..
- Pajvani U, Shawber C, Samuel V, Birkenfeld A, Shulman G, Kitajewski J, et al. Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nat Med. 2011;17:961-7 pubmed publisher..The data identify a heretofore unknown metabolic function of Notch and suggest that Notch inhibition is beneficial in diabetes treatment, in part by helping to offset excessive FoxO1-driven hepatic glucose production. ..
- Castellanos Rivera R, Monteagudo M, Pentz E, Glenn S, Gross K, Carretero O, et al. Transcriptional regulator RBP-J regulates the number and plasticity of renin cells. Physiol Genomics. 2011;43:1021-8 pubmed publisher..We conclude that RBP-J is required to maintain basal renin expression and the ability of smooth muscle cells along the kidney vasculature to regain the renin phenotype, a fundamental mechanism to preserve homeostasis. ..
- Hu X, Chung A, Wu I, Foldi J, Chen J, Ji J, et al. Integrated regulation of Toll-like receptor responses by Notch and interferon-gamma pathways. Immunity. 2008;29:691-703 pubmed publisher..These findings identify new immune functions for RBP-J, Hes, and Hey proteins and provide insights into mechanisms by which Notch, TLR, and IFN-gamma signals are integrated to modulate specific effector functions in macrophages. ..
- Demehri S, Liu Z, Lee J, Lin M, Crosby S, Roberts C, et al. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity. PLoS Biol. 2008;6:e123 pubmed publisher..These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations. ..
- Pajvani U, Qiang L, Kangsamaksin T, Kitajewski J, Ginsberg H, Accili D. Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability. Nat Med. 2013;19:1054-60 pubmed publisher..These data identify Notch as a therapeutically actionable branch point of metabolic signaling at which Akt activation in the liver can be uncoupled from hepatosteatosis. ..
- Morimoto M, Liu Z, Cheng H, Winters N, Bader D, Kopan R. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate. J Cell Sci. 2010;123:213-24 pubmed publisher..These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals. ..
- Demehri S, Morimoto M, Holtzman M, Kopan R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol. 2009;7:e1000067 pubmed publisher..Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients. ..
- van Es J, van Gijn M, Riccio O, van den Born M, Vooijs M, Begthel H, et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005;435:959-63 pubmed..Our data indicate that gamma-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease. ..
- Wang Y, He F, Feng F, Liu X, Dong G, Qin H, et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 2010;70:4840-9 pubmed publisher..These results provide new insights into the molecular mechanisms of macrophage polarization and shed light on new therapies for cancers through the modulation of macrophage polarization through the Notch signaling...
- Barrantes I, Elia A, Wunsch K, Hrabe de Angelis M, Mak T, Rossant J, et al. Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse. Curr Biol. 1999;9:470-80 pubmed..In this region, Notch function activates a set of genes that are involved in boundary formation and anterior-posterior somite identity. ..
- Cheng H, Kim M, Valerius M, Surendran K, Schuster Gossler K, Gossler A, et al. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007;134:801-11 pubmed..These results establish distinct (non-redundant), instructive roles for Notch receptors in nephron segmentation. ..
- Tao J, Chen S, Yang T, Dawson B, Munivez E, Bertin T, et al. Osteosclerosis owing to Notch gain of function is solely Rbpj-dependent. J Bone Miner Res. 2010;25:2175-83 pubmed publisher..Importantly, selective deletion of a Notch nuclear effector--Rbpj--in osteoblasts completely suppressed the osteosclerotic and growth-retardation phenotypes...
- Han H, Tanigaki K, Yamamoto N, Kuroda K, Yoshimoto M, Nakahata T, et al. Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int Immunol. 2002;14:637-45 pubmed..Myeloid and B lineage differentiation appears normal in the bone marrow of RBP-J-inactivated mice. These results suggest that RBP-J, probably by mediating Notch signaling, controls T versus B cell fate decision in lymphoid progenitors. ..
- Lewis K, Caton M, Bogunovic M, Greter M, Grajkowska L, Ng D, et al. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity. 2011;35:780-91 pubmed publisher..Thus, Notch2 is a common differentiation signal for T cell-priming CD11b(+) DC subsets in the spleen and intestine. ..
- Hsu F, Pajerowski A, Nelson Holte M, Sundsbak R, Shapiro V. NKAP is required for T cell maturation and acquisition of functional competency. J Exp Med. 2011;208:1291-304 pubmed publisher..This defect is not simply in cell survival, as the T cell maturation defect was not rescued by a Bcl-2 transgene. Thus, NKAP is required for T cell maturation and the acquisition of functional competency. ..
- Julian E, Dave R, Robson J, Hallahan A, Wainwright B. Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma. Oncogene. 2010;29:3465-76 pubmed publisher..Hedgehog-dependent medulloblastoma were not blocked by loss of RBP-J, indicating that canonical Notch signaling is not required for tumor initiation and growth in this model. ..
- Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T. LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Mol Cell Biol. 1998;18:644-54 pubmed..KyoT2 is a novel negative regulatory molecule for RBP-J-mediated transcription in mammalian systems. ..
- Fang T, Yashiro Ohtani Y, Del Bianco C, Knoblock D, Blacklow S, Pear W. Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity. 2007;27:100-10 pubmed..Together, these data implicate Gata3 as a direct transcriptional Notch target that acts in concert with Notch signaling to generate optimal Th2 cell responses. ..
- Wall D, Mears A, McNeill B, Mazerolle C, Thurig S, Wang Y, et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol. 2009;184:101-12 pubmed publisher..This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior. ..
- Tanigaki K, Han H, Yamamoto N, Tashiro K, Ikegawa M, Kuroda K, et al. Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nat Immunol. 2002;3:443-50 pubmed..In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria. ..
- Benedito R, Rocha S, Woeste M, Zamykal M, Radtke F, Casanovas O, et al. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling. Nature. 2012;484:110-4 pubmed publisher..We propose that successful anti-angiogenic targeting of these receptors and their ligands will strongly depend on the status of endothelial Notch signalling. ..
- del Monte G, Grego Bessa J, González Rajal A, Bolós V, de la Pompa J. Monitoring Notch1 activity in development: evidence for a feedback regulatory loop. Dev Dyn. 2007;236:2594-614 pubmed..We found that Notch1 transcription and activity was severely reduced in zebrafish and mouse Notch pathway mutants, suggesting that vertebrate Notch1 expression is regulated by a positive feedback loop. ..
- Costa R, Honjo T, Silva A. Learning and memory deficits in Notch mutant mice. Curr Biol. 2003;13:1348-54 pubmed
- Alam M, Maekawa Y, Kitamura A, Tanigaki K, Yoshimoto T, Kishihara K, et al. Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2010;107:5943-8 pubmed publisher..Our studies identify a Notch-AhR axis that regulates IL-22 expression and fine-tunes immune system control of inflammatory responses. ..
- Hamidi H, Gustafason D, Pellegrini M, Gasson J. Identification of novel targets of CSL-dependent Notch signaling in hematopoiesis. PLoS ONE. 2011;6:e20022 pubmed publisher..Time course analysis of hematopoietic development revealed that cells with Notch 1 overexpression mimic miRNA expression of cells in a less mature stage, which is consistent with our previous biological characterization. ..
- Minoguchi S, Taniguchi Y, Kato H, Okazaki T, Strobl L, Zimber Strobl U, et al. RBP-L, a transcription factor related to RBP-Jkappa. Mol Cell Biol. 1997;17:2679-87 pubmed..This is again in contrast to physical association of RBP-J with EBNA-2. Several models to explain functional interaction between RBP-L and EBNA-2 are discussed. ..
- Souilhol C, Cormier S, Tanigaki K, Babinet C, Cohen Tannoudji M. RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development. Mol Cell Biol. 2006;26:4769-74 pubmed..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...
- Amsen D, Blander J, Lee G, Tanigaki K, Honjo T, Flavell R. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell. 2004;117:515-26 pubmed..Notch directs Th2 differentiation by inducing GATA3 and by directly regulating il4 gene transcription through RBPJkappa sites in a 3' enhancer. ..
- Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Gotz M, et al. Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell. 2010;6:445-56 pubmed publisher..The discovery of multiple NSC populations with Notch dependence but selective responses to stimuli and reversible quiescence has important implications for the mechanisms of adaptive learning and also for regenerative therapy. ..
- Boggs K, Henderson B, Reisman D. RBP-Jkappa binds to and represses transcription of the p53 tumor suppressor gene. Cell Biol Int. 2009;33:318-24 pubmed publisher..Because defects in the Notch signaling pathway have been implicated in carcinogenesis, aberrant RBP-Jkappa expression and deregulated regulation of the p53 tumor suppressor could be an important step in some forms of cancers. ..
- Niwa Y, Masamizu Y, Liu T, Nakayama R, Deng C, Kageyama R. The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock. Dev Cell. 2007;13:298-304 pubmed..We thus propose that Hes7 oscillation is initiated by Fgf signaling and propagated/maintained anteriorly by Notch signaling. ..
- Kwon C, Cheng P, King I, Andersen P, Shenje L, Nigam V, et al. Notch post-translationally regulates ?-catenin protein in stem and progenitor cells. Nat Cell Biol. 2011;13:1244-51 pubmed publisher..It did, however, require the endocytic adaptor protein Numb and lysosomal activity. This study reveals a previously unrecognized function of Notch in negatively titrating active ?-catenin protein levels in stem and progenitor cells. ..
- Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U, Espinosa L, et al. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology. 2011;140:1230-1240.e1-7 pubmed publisher..Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4)...
- Dale J, Malapert P, Chal J, Vilhais Neto G, Maroto M, Johnson T, et al. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev Cell. 2006;10:355-66 pubmed..Thus, Snail genes define a class of cyclic genes that coordinate segmentation and PSM morphogenesis. ..
- de la Pompa J, Wakeham A, Correia K, Samper E, Brown S, Aguilera R, et al. Conservation of the Notch signalling pathway in mammalian neurogenesis. Development. 1997;124:1139-48 pubmed..Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation. ..
- Hu X, Feng F, Wang Y, Wang L, He F, Dou G, et al. Blockade of Notch signaling in tumor-bearing mice may lead to tumor regression, progression, or metastasis, depending on tumor cell types. Neoplasia. 2009;11:32-8 pubmed
- Masui T, Long Q, Beres T, Magnuson M, Macdonald R. Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex. Genes Dev. 2007;21:2629-43 pubmed..We show that early in pancreatic development, active PTF1a requires interaction with RBPJ, the vertebrate Suppressor of Hairless, within a stable trimeric DNA-binding complex (PTF1)...
- Krebs L, Iwai N, Nonaka S, Welsh I, Lan Y, Jiang R, et al. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev. 2003;17:1207-12 pubmed..Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. ..
- Schroeder T, Fraser S, Ogawa M, Nishikawa S, Oka C, Bornkamm G, et al. Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis. Proc Natl Acad Sci U S A. 2003;100:4018-23 pubmed..Repression over the cardiogenic pathway was restored by expressing RBP-J in RBP-J-deficient ES cells. Our data indicate that Notch signaling via RBP-J plays an important role for the correct specification of myocardial cell fates. ..
- Zhao B, Grimes S, Li S, Hu X, Ivashkiv L. TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J. J Exp Med. 2012;209:319-34 pubmed publisher..These findings identify RBP-J as a key upstream negative regulator of osteoclastogenesis that restrains excessive bone resorption in inflammatory settings. ..
- Ferjentsik Z, Hayashi S, Dale J, Bessho Y, Herreman A, De Strooper B, et al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009;5:e1000662 pubmed publisher..embryos carrying a mutation in different components of the Notch pathway, such as Lunatic fringe (Lfng), Hes7, Rbpj, and presenilin1/presenilin2 (Psen1/Psen2), and by pharmacological blocking of the Notch pathway...
- Tamura K, Taniguchi Y, Minoguchi S, Sakai T, Tun T, Furukawa T, et al. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Curr Biol. 1995;5:1416-23 pubmed..RBP-J kappa/Su(H) does not appear to interact with Notch via the CDC10/ankyrin repeats implicated in previous studies. ..
- Yamamoto N, Tanigaki K, Han H, Hiai H, Honjo T. Notch/RBP-J signaling regulates epidermis/hair fate determination of hair follicular stem cells. Curr Biol. 2003;13:333-8 pubmed..These results suggest that Notch/RBP-J signaling regulates the cell fate determination of hair follicular stem cells at the bulge region. ..
- Kuroda K, Han H, Tani S, Tanigaki K, Tun T, Furukawa T, et al. Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity. 2003;18:301-12 pubmed..MINT may serve as a functional homolog of Drosophila Hairless. ..
- Taylor M, Yeager K, Morrison S. Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems. Development. 2007;134:2435-47 pubmed..To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS progenitors using Wnt1-Cre or Nestin-Cre...
- Woodhoo A, Alonso M, Droggiti A, Turmaine M, D Antonio M, Parkinson D, et al. Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity. Nat Neurosci. 2009;12:839-47 pubmed publisher..These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesis. ..
- Tsao P, Vasconcelos M, Izvolsky K, Qian J, LU J, Cardoso W. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009;136:2297-307 pubmed publisher..We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling...
- Komine O, Nagaoka M, Watase K, Gutmann D, Tanigaki K, Honjo T, et al. The monolayer formation of Bergmann glial cells is regulated by Notch/RBP-J signaling. Dev Biol. 2007;311:238-50 pubmed..Thus, Notch-RBP-J signaling plays crucial roles in the monolayer formation and morphogenesis of Bergmann glia. ..
- Buono K, Robinson G, Martin C, Shi S, Stanley P, Tanigaki K, et al. The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy. Dev Biol. 2006;293:565-80 pubmed..We propose that the Notch-RBP-J pathway regulates alveolar development during pregnancy by maintaining luminal cell fate and preventing uncontrolled basal cell proliferation. ..
- Laky K, Fowlkes B. Presenilins regulate alphabeta T cell development by modulating TCR signaling. J Exp Med. 2007;204:2115-29 pubmed
- Amsen D, Antov A, Jankovic D, Sher A, Radtke F, Souabni A, et al. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity. 2007;27:89-99 pubmed..Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch. ..
- Shi M, Hu Z, Zheng M, Song N, Huang Y, Zhao G, et al. Notch-Rbpj signaling is required for the development of noradrenergic neurons in the mouse locus coeruleus. J Cell Sci. 2012;125:4320-32 pubmed publisher..We report here that Rbpj, a key nuclear effector in the Notch signaling pathway, plays an essential role in LC neuron development in the ..