immunoglobulin j recombination signal sequence binding protein


Summary: A ubiquitously expressed sequence-specific transcriptional repressor that is normally the target of signaling by NOTCH PROTEINS.

Top Publications

  1. Gross H, Barth S, Palermo R, Mamiani A, Hennard C, Zimber Strobl U, et al. Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting. Virology. 2010;397:299-310 pubmed publisher
  2. 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. ..
  3. 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. ..
  4. Johnson S, Ilagan M, Kopan R, Barrick D. Thermodynamic analysis of the CSL x Notch interaction: distribution of binding energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of competition with the viral transactivator EBNA2. J Biol Chem. 2010;285:6681-92 pubmed publisher
  5. Hayata T, Blitz I, Iwata N, Cho K. Identification of embryonic pancreatic genes using Xenopus DNA microarrays. Dev Dyn. 2009;238:1455-66 pubmed publisher
    ..Our analyses implicate the involvement of previously unsuspected signaling pathways during early pancreas development. Developmental Dynamics 238:1455-1466, 2009. (c) 2009 Wiley-Liss, Inc. ..
  6. Foldi J, Chung A, Xu H, Zhu J, Outtz H, Kitajewski J, et al. Autoamplification of Notch signaling in macrophages by TLR-induced and RBP-J-dependent induction of Jagged1. J Immunol. 2010;185:5023-31 pubmed publisher
    ..Early and direct cooperation between TLR and Notch pathways leads to Jagged1-RBP-J-mediated autoamplification of Notch signaling that can modulate later phases of the TLR response...
  7. Heinzelmann K, Scholz B, Nowak A, Fossum E, Kremmer E, Haas J, et al. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4/K10) is a novel interaction partner of CSL/CBF1, the major downstream effector of Notch signaling. J Virol. 2010;84:12255-64 pubmed publisher
    ..Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling...
  8. 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...
  9. Dong Y, Jesse A, Kohn A, Gunnell L, Honjo T, Zuscik M, et al. RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development. 2010;137:1461-71 pubmed publisher
    ..Finally, Hes1 was identified as an RBPjkappa-dependent Notch target gene important for MPC maintenance and the suppression of in vitro chondrogenesis. ..

More Information


  1. Tanaka M, Setoguchi T, Hirotsu M, Gao H, Sasaki H, Matsunoshita Y, et al. Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation. Br J Cancer. 2009;100:1957-65 pubmed publisher
  2. Cruickshank M, Fenwick E, Karimi M, Abraham L, Ulgiati D. Cell- and stage-specific chromatin structure across the Complement receptor 2 (CR2/CD21) promoter coincide with CBF1 and C/EBP-beta binding in B cells. Mol Immunol. 2009;46:2613-22 pubmed publisher
  3. Fujimoto M, Takagi Y, Muraki K, Nozaki K, Yamamoto N, Tsuji M, et al. RBP-J promotes neuronal differentiation and inhibits oligodendroglial development in adult neurogenesis. Dev Biol. 2009;332:339-50 pubmed publisher
    ..The defects in maturation of RBP-J-deficient neurons could be partly rescued by knockdown of Olig2 in vivo. Our findings suggest that RBP-J might regulate neuronal maturation at least in part through transcriptional repression of Olig2. ..
  4. 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. ..
  5. Liu X, Yan S, Abecassis M, Hummel M. Biphasic recruitment of transcriptional repressors to the murine cytomegalovirus major immediate-early promoter during the course of infection in vivo. J Virol. 2010;84:3631-43 pubmed publisher
    ..The observation that repressors are bound to the MIEP and other promoters immediately upon infection suggests that latency may be established in some cells very early in infection. ..
  6. Kis L, Salamon D, Persson E, Nagy N, Scheeren F, Spits H, et al. IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter. Proc Natl Acad Sci U S A. 2010;107:872-7 pubmed publisher
    ..In light of the fact that IL-21 is already in clinical trials for the treatment of multiple malignancies, the in vivo modulation of EBV gene expression by IL-21 might have therapeutic benefits for the EBV-carrying malignancies...
  7. Riesenberg A, Liu Z, Kopan R, Brown N. Rbpj cell autonomous regulation of retinal ganglion cell and cone photoreceptor fates in the mouse retina. J Neurosci. 2009;29:12865-77 pubmed publisher
    ..2006b; Yaron et al., 2006), Notch3, and Hes1 mutants. We found particular combinations of Notch pathway genes regulate the development of each retinal cell type. ..
  8. Persson L, Wilson A. Wide-scale use of Notch signaling factor CSL/RBP-Jkappa in RTA-mediated activation of Kaposi's sarcoma-associated herpesvirus lytic genes. J Virol. 2010;84:1334-47 pubmed publisher
    ..These findings broaden the role for CSL in coordinating the KSHV lytic gene expression program and help to define a signature motif for functional CSL sites within the viral genome. ..
  9. Mercher T, Raffel G, Moore S, Cornejo M, Baudry Bluteau D, Cagnard N, et al. The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model. J Clin Invest. 2009;119:852-64 pubmed publisher
  10. Fior R, Henrique D. "Notch-Off": a perspective on the termination of Notch signalling. Int J Dev Biol. 2009;53:1379-84 pubmed publisher
    ..We further highlight the importance of properly terminating Notch activity during cell fate decisions mediated by this pathway. ..
  11. Gao F, Zhang Q, Zheng M, Liu H, Hu Y, Zhang P, et al. Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors. Mol Cell Neurosci. 2009;40:442-50 pubmed publisher
    ..These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCs into INPs and support the generation of certain early born neurons at early neurogenic stages. ..
  12. Borggrefe T, Oswald F. The Notch signaling pathway: transcriptional regulation at Notch target genes. Cell Mol Life Sci. 2009;66:1631-46 pubmed publisher
    ..We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer. ..
  13. King I, Kathiriya I, Murakami M, Nakagawa M, Gardner K, Srivastava D, et al. Hrt and Hes negatively regulate Notch signaling through interactions with RBP-Jkappa. Biochem Biophys Res Commun. 2006;345:446-52 pubmed
    ..These findings suggest a novel mechanism for negative feedback on Notch signaling that requires RBP-Jkappa to interact physically with Hrt and Hes. ..
  14. Yamamizu K, Matsunaga T, Uosaki H, Fukushima H, Katayama S, Hiraoka Kanie M, et al. Convergence of Notch and beta-catenin signaling induces arterial fate in vascular progenitors. J Cell Biol. 2010;189:325-38 pubmed publisher
    ..This molecular machinery for arterial specification leads to an integrated and more comprehensive understanding of vascular signaling. ..
  15. 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
    ..These results demonstrate that physiological Notch signaling is required for gliogenesis in vivo, independent of the role of Notch in the maintenance of undifferentiated neural progenitors. ..
  16. Polson A, Takahashi P, Reisman D. ChIP (chromatin immunoprecipitation) analysis demonstrates co-ordinated binding of two transcription factors to the promoter of the p53 tumour-suppressor gene. Cell Biol Int. 2010;34:883-91 pubmed publisher
    ..Here, we demonstrate through the use of chromatin immunoprecipitation (ChIP) assays that the co-ordinated binding of these two factors to the p53 promoter occurs in vivo and serves to regulate p53's activity during the cell cycle. ..
  17. Liefke R, Oswald F, Alvarado C, Ferres Marco D, Mittler G, Rodriguez P, et al. Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex. Genes Dev. 2010;24:590-601 pubmed publisher
    ..KDM5A interacts physically with RBP-J; this interaction is conserved in Drosophila and is crucial for Notch-induced growth and tumorigenesis responses. ..
  18. Hu B, Lefort K, Qiu W, Nguyen B, Rajaram R, Castillo E, et al. Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis. Genes Dev. 2010;24:1519-32 pubmed publisher
    ..Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators. ..
  19. 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
    ..These results indicated an absolute requirement of Notch signaling for the maintenance of neural stem cells and a proper control of neurogenesis in both embryonic and adult brains. ..
  20. Morrow D, Cullen J, Liu W, Cahill P, Redmond E. Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway. Arterioscler Thromb Vasc Biol. 2010;30:2597-603 pubmed publisher
    ..To determine the role of Notch signaling in mediating alcohol's inhibition of smooth muscle cell (SMC) proliferation...
  21. Sanalkumar R, Indulekha C, Divya T, Divya M, Anto R, Vinod B, et al. ATF2 maintains a subset of neural progenitors through CBF1/Notch independent Hes-1 expression and synergistically activates the expression of Hes-1 in Notch-dependent neural progenitors. J Neurochem. 2010;113:807-18 pubmed publisher
  22. Ehm O, Goritz C, Covic M, Schäffner I, Schwarz T, Karaca E, et al. RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci. 2010;30:13794-807 pubmed publisher
    ..These results identify RBPJ?-dependent pathways as essential regulators of adult neural stem cell maintenance and suggest that the actions of RBPJ? are, at least in part, mediated by control of Sox2 expression. ..
  23. Surendran K, Boyle S, Barak H, Kim M, Stomberski C, McCright B, et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol. 2010;337:386-95 pubmed publisher
  24. Gustafson T, Wellberg E, Laffin B, Schilling L, Metz R, Zahnow C, et al. Ha-Ras transformation of MCF10A cells leads to repression of Singleminded-2s through NOTCH and C/EBPbeta. Oncogene. 2009;28:1561-8 pubmed publisher
    ..These studies illustrate a novel pathway of tumor suppressor gene silencing in Ha-Ras-transformed breast epithelial cells and identify SIM2s as a target of C/EBPbeta and NOTCH signaling. ..
  25. Agrawal S, Archer C, Schaffer D. Computational models of the Notch network elucidate mechanisms of context-dependent signaling. PLoS Comput Biol. 2009;5:e1000390 pubmed publisher
    ..This work thus helps our understanding of an important cell fate control system and begins to elucidate how this context dependent signaling system can be modulated in different cellular settings to exhibit entirely different behaviors. ..
  26. Hao L, Rizzo P, Osipo C, Pannuti A, Wyatt D, Cheung L, et al. Notch-1 activates estrogen receptor-alpha-dependent transcription via IKKalpha in breast cancer cells. Oncogene. 2010;29:201-13 pubmed publisher
    ..Our observations suggest that a hitherto unknown Notch-1/ERalpha chromatin crosstalk mediates Notch signaling effects in ERalpha-positive breast cancer cells and contributes to regulate the transcriptional functions of ERalpha itself. ..
  27. Lee S, Sakakibara S, Maruo S, Zhao B, Calderwood M, Holthaus A, et al. Epstein-Barr virus nuclear protein 3C domains necessary for lymphoblastoid cell growth: interaction with RBP-Jkappa regulates TCL1. J Virol. 2009;83:12368-77 pubmed publisher
    ..We have confirmed that EBNA3C upregulates TCL1 and discovered that EBNA3C upregulates TCL1 through RBP-Jkappa, indicating a central role for EBNA3C interaction with RBP-Jkappa in mediating cell gene transcription...
  28. Masui T, Swift G, Deering T, Shen C, Coats W, Long Q, et al. Replacement of Rbpj with Rbpjl in the PTF1 complex controls the final maturation of pancreatic acinar cells. Gastroenterology. 2010;139:270-80 pubmed publisher
  29. Niranjan T, Bielesz B, Gruenwald A, Ponda M, Kopp J, Thomas D, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008;14:290-8 pubmed publisher
    ..Collectively, our observations suggest that Notch activation in mature podocytes is a new mechanism in the pathogenesis of glomerular disease and thus could represent a new therapeutic target. ..
  30. Maruo S, Wu Y, Ito T, Kanda T, Kieff E, Takada K. Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth. Proc Natl Acad Sci U S A. 2009;106:4419-24 pubmed publisher
  31. Moellering R, Cornejo M, Davis T, Del Bianco C, Aster J, Blacklow S, et al. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009;462:182-8 pubmed publisher
    ..Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL. ..
  32. 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. ..
  33. Wang S, Chen L, Chen L, Tsai H, Shih Y, Yang C, et al. Transcriptional regulation of the ORF61 and ORF60 genes of Kaposi's sarcoma-associated herpesvirus. Virology. 2010;397:311-21 pubmed publisher
    ..Our results provide further insights into the regulatory network of the viral lytic genes in KSHV reactivation. ..
  34. Henke R, Savage T, Meredith D, Glasgow S, Hori K, Dumas J, et al. Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development. 2009;136:2945-54 pubmed publisher
  35. Gao J, Chen Y, Wu K, Liu J, Zhao Y, Pan Y, et al. RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells. Exp Cell Res. 2010;316:149-57 pubmed publisher
    ..Taken together, these findings indicate that RUNX3 suppresses Notch signaling in HCC SMMC7721 cells by its interaction with ICN1 and thus recruitment to the RBP-J recognition motif of downstream genes of Notch signaling. ..
  36. Chang P, Boonsiri J, Wang S, Chen L, Miller G. Binding of RBP-Jkappa (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein. Virology. 2010;398:38-48 pubmed publisher
    ..All bound RBP-Jkappa, but only one responded robustly to ORF50 protein. We propose models for the possible function of ancillary sequences flanking the RBP-Jkappa-binding element which are crucial for mediating ORF50 transactivation. ..
  37. Friedmann D, Kovall R. Thermodynamic and structural insights into CSL-DNA complexes. Protein Sci. 2010;19:34-46 pubmed publisher
    ..Taken together, our results provide a quantitative and biophysical basis for understanding how CSL interacts with DNA sites in vivo. ..
  38. Izumiya Y, Izumiya C, Hsia D, Ellison T, Luciw P, Kung H. NF-kappaB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator. J Virol. 2009;83:4435-46 pubmed publisher
    ..An important feature of this model is that the interplay between RBP-Jkappa and NF-kappaB on viral promoters controls viral gene expression mediated by K-Rta. ..
  39. Tanigaki K, Honjo T. Two opposing roles of RBP-J in Notch signaling. Curr Top Dev Biol. 2010;92:231-52 pubmed publisher
    ..Finally, the Notch-independent function of RBP-J was recently discovered and will be reviewed here. ..
  40. Ishitani T, Hirao T, Suzuki M, Isoda M, Ishitani S, Harigaya K, et al. Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex. Nat Cell Biol. 2010;12:278-85 pubmed publisher
    ..Our results both define a new function for NLK and reveal a previously unidentified mode of regulation in the Notch signalling pathway. ..
  41. Perumalsamy L, Nagala M, Banerjee P, Sarin A. A hierarchical cascade activated by non-canonical Notch signaling and the mTOR-Rictor complex regulates neglect-induced death in mammalian cells. Cell Death Differ. 2009;16:879-89 pubmed publisher
    ..Thus, this study identifies a non-canonical signaling cascade wherein NIC integrates with multiple pathways to regulate cell survival. ..
  42. Sanalkumar R, Dhanesh S, James J. Non-canonical activation of Notch signaling/target genes in vertebrates. Cell Mol Life Sci. 2010;67:2957-68 pubmed publisher
    ..Here, we have tried to congregate the reports that describe the non-canonical/CBF1-independent Notch signaling and target gene activation in vertebrates with specific emphasis on their functional relevance. ..
  43. Wang S, Kawashima N, Sakamoto K, Katsube K, Umezawa A, Suda H. Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is promoted by mammalian transcriptional repressor Rbpj. Biochem Biophys Res Commun. 2010;400:39-45 pubmed publisher
    ..Histological findings revealed that expression of Rbpj was primarily observed in osteoblasts. These results suggest that Rbpj may play essential roles in osteoblast differentiation. ..
  44. Ferrari Toninelli G, Bonini S, Uberti D, Napolitano F, Stante M, Santoro F, et al. Notch activation induces neurite remodeling and functional modifications in SH-SY5Y neuronal cells. Dev Neurobiol. 2009;69:378-91 pubmed publisher
  45. Chari S, Umetsu S, Winandy S. Notch target gene deregulation and maintenance of the leukemogenic phenotype do not require RBP-J kappa in Ikaros null mice. J Immunol. 2010;185:410-7 pubmed publisher
  46. 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. ..
  47. 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. ..
  48. Shimizu T, Tanaka T, Iso T, Doi H, Sato H, Kawai Kowase K, et al. Notch signaling induces osteogenic differentiation and mineralization of vascular smooth muscle cells: role of Msx2 gene induction via Notch-RBP-Jk signaling. Arterioscler Thromb Vasc Biol. 2009;29:1104-11 pubmed publisher
    ..These results imply a new mechanism for osteogenic differentiation of vascular SMCs in which Notch/RBP-Jk signaling directly induces Msx2 gene expression and suggest its crucial role in mediating vascular calcification. ..
  49. Feng F, Wang Y, Hu X, Liu X, Ji G, Chen Y, et al. The transcription factor RBP-J-mediated signaling is essential for dendritic cells to evoke efficient anti-tumor immune responses in mice. Mol Cancer. 2010;9:90 pubmed publisher
    ..The Notch signaling pathway might be a target for the establishment of the DC-based anti-tumor immunotherapies. ..
  50. Whelan J, Kellogg A, Shewchuk B, Hewan Lowe K, Bertrand F. Notch-1 signaling is lost in prostate adenocarcinoma and promotes PTEN gene expression. J Cell Biochem. 2009;107:992-1001 pubmed publisher
    ..These data collectively indicate that defects in Notch-1 signaling may play a role in human prostate tumor formation in part via a mechanism that involves regulation of the PTEN tumor suppressor gene. ..
  51. Katoh Y, Katoh M. Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. Int J Oncol. 2009;35:187-92 pubmed
    ..Together these facts indicate that Hedgehog, TGFbeta, and RTK signals positively regulate GLI1, and that Notch, and GsPCR signals negatively regulate the GLI1. ..
  52. Wang L, Wang Y, Hu X, Zhang B, Dou G, He F, et al. Notch-RBP-J signaling regulates the mobilization and function of endothelial progenitor cells by dynamic modulation of CXCR4 expression in mice. PLoS ONE. 2009;4:e7572 pubmed publisher
    ..Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases. ..