Pathway maps

Development_NOTCH1-mediated pathway for NF-KB activity modulation
Development_NOTCH1-mediated pathway for NF-KB activity modulation

Object List (links open in MetaCore):

MEKK1(MAP3K1), Histone deacetylase class I, IRAK1/2, TRAF6, MAML1, NFKBIA, Histone H3, PCAF, NOTCH1 receptor = NOTCH1 (NEXT), ADAM17, NOTCH1 (NICD), IL-1 alpha, p300, NOTCH1 receptor, gamma-Secretase complex, HDAC2, IKK (cat), NOTCH1(NEXT) = NOTCH1(NICD), NF-kB, SKIP (Ski-interacting protein), SAP30, IL-1RI, CIR, N-CoR, DLL1, RBP-J kappa (CBF1), NOTCH1 (NEXT), NF-kB, NFKBIA, NIK(MAP3K14), c-Rel (NF-kB subunit), SMRT, HDAC1, Jagged1, I-kB, Histone H4

Description

NOTCH1-mediated pathway for NF-KB activity modulation

Interleukin 1 ( IL-1 ) activates Nuclear factor of kappa light polypeptide gene enhancer in B-cells ( NF-KB ) via Interleukin-1 receptor-associated kinase ( IRAK ) and Mitogen-activated protein kinase kinase kinase 1 ( MEKK1(MAP3K1) )-dependent inhibition of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor ( I-kB ) [1], [2]. V-rel reticuloendotheliosis viral oncogene homolog ( c-Rel (NF-kB subunit) ) can trigger Notch homolog 1 translocation-associated ( NOTCH1 receptor ) signaling pathway by inducing expression of Jagged1, ligand for Notch receptors [3], [4]. NOTCH1 receptor activated by Jagged1 or Delta-like 1 ( DLL1 ) is cleaved by ADAM metallopeptidase domain 17 ( ADAM17 ) and Presenilin1 to intracellular domain of NOTCH1 ( NOTCH1 (NICD) ). NOTCH1 (NICD) is transported to nucleus and participates in recombination signal binding protein for immunoglobulin kappa J region ( RBP-J kappa (CBF1) )-mediated transcription [5], [4].

RBP-J kappa (CBF1) can act as transcription repressor or activator, depending on protein complex, which it recruits to DNA [6], [7], [8]. RBP-J kappa (CBF1) acts as gene repressor in a complex with co-repressors Nuclear receptor co-repressor 2 ( SMRT )/Nuclear receptor co-repressor 1 ( N-CoR )/ Histone deacetylase 1 ( HDAC1 ) [9], [7] or CBF1 interacting corepressor ( CIR )/ Sin3A-associated protein 30kDa ( SAP30 )/ Histone deacetylase 2 ( HDAC2 ) [9], [7]. HDAC participates in histone deacetylation, which prevents transcription. SMRT and CIR function act as linkers between HDAC and RBP-J kappa (CBF1) via direct binding of linker protein SNW domain containing 1 ( SKIP ) [10], [9], [11], [6]. Intracellular domain of Notch homolog 1 translocation-associated ( NOTCH1 (NICD) ) binding to SKIP competes with SMRT [6] and, possibly, CIR [7]. NOTCH1 (NICD) recruits Mastermind-like 1 ( MAML1 ), which facilitates E1A binding protein p300 ( p300 ) recruitment. The latter in turn facilitates p300/CBP-associated factor ( PCAF ) recruitment. Complex MAML1/ p300/ PCAF acts as histone acetylase and assist chromatin remodeling. NOTCH1 (NICD) competition with RBP-J kappa (CBF1) corepressors determines positive regulation of transcription by NOTCH1 (NICD).

This pathway enables NOTCH1 (NICD) activation of transcription of Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha ( NFKBIA ) and thus lowers NF-KB activity [4].

References:

  1. Renard P, Raes M
    The proinflammatory transcription factor NFkappaB: a potential target for novel therapeutical strategies. Cell biology and toxicology 1999;15(6):341-4
  2. Yao J, Kim TW, Qin J, Jiang Z, Qian Y, Xiao H, Lu Y, Qian W, Gulen MF, Sizemore N, DiDonato J, Sato S, Akira S, Su B, Li X
    Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFkappaB activation pathways bifurcate at IL-1 receptor-associated kinase modification. The Journal of biological chemistry 2007 Mar 2;282(9):6075-89
  3. Bash J, Zong WX, Banga S, Rivera A, Ballard DW, Ron Y, Gelinas C
    Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. The EMBO journal 1999 May 17;18(10):2803-11
  4. Osipo C, Golde TE, Osborne BA, Miele LA
    Off the beaten pathway: the complex cross talk between Notch and NF-kappaB. Laboratory investigation; a journal of technical methods and pathology 2008 Jan;88(1):11-7
  5. Bolos V, Grego-Bessa J, de la Pompa JL
    Notch signaling in development and cancer. Endocrine reviews 2007 May;28(3):339-63
  6. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD
    SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function. Molecular and cellular biology 2000 Apr;20(7):2400-10
  7. Mumm JS, Kopan R
    Notch signaling: from the outside in. Developmental biology 2000 Dec 15;228(2):151-65
  8. Kopan R
    Notch: a membrane-bound transcription factor. Journal of cell science 2002 Mar 15;115(Pt 6):1095-7
  9. Hsieh JJ, Zhou S, Chen L, Young DB, Hayward SD
    CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex. Proceedings of the National Academy of Sciences of the United States of America 1999 Jan 5;96(1):23-8
  10. Kao HY, Ordentlich P, Koyano-Nakagawa N, Tang Z, Downes M, Kintner CR, Evans RM, Kadesch T
    A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes & development 1998 Aug 1;12(15):2269-77
  11. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD
    A role for SKIP in EBNA2 activation of CBF1-repressed promoters. Journal of virology 2000 Feb;74(4):1939-47