Abstract
The highly conserved Notch signal transduction pathway orchestrates fundamental cellular processes including, differentiation, proliferation, and apoptosis during embryonic development and in the adult organism. Dysregulated Notch signaling underlies the etiology of a variety of human diseases, such as certain types of cancers, developmental disorders and cardiovascular disease. Ligand binding induces proteolytic cleavage of the Notch receptor and nuclear translocation of the Notch intracellular domain (NICD), which forms a ternary complex with the transcription factor CSL and the coactivator MAML to upregulate transcription of Notch target genes. The DNA-binding protein CSL is the centrepiece of transcriptional regulation in the Notch pathway, acting as a molecular hub for interactions with either corepressors or coactivators to repress or activate, respectively, transcription. Here we review previous structure-function studies of CSL-associated coregulator complexes and discuss the molecular insights gleaned from this research. We discuss the functional consequences of both activating and repressing binding partners using the same interaction platforms on CSL. We also emphasize that although there has been a significant uptick in structural information over the past decade, it is still under debate how the molecular switch from repression to activation mediated by CSL occurs at Notch target genes and whether it will be possible to manipulate these transcription complexes therapeutically in the future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- CBF1:
-
C-promoter Binding Factor 1
- LAG-1:
-
abnormal cell LINeage-12 (Lin-12) And abnormal Germ line proliferation phenotype-1 (Glp-1)
- RBP-J:
-
Recombination Signal-Binding Protein for immunoglobin kappa J region
- Su(H):
-
Suppressor of Hairless
- CBP/CREBBP:
-
C-Adenosine Mono Phosphate Responsive Element (cAMP-RE)-Binding protein (CREB)-Binding Protein; KAT3A
- EP300:
-
E1A Binding Protein P300, KAT3B
- PCAF:
-
P300/CBP-Associated Factor; KAT2B
- GCN5:
-
General Control Of AmiNo Acid Synthesis Protein 5-Like 2; KAT2A
- CDK8:
-
Cyclin-Dependent Kinase 8
- SCF:
-
S-Phase Kinase Associated Protein1/Cullin/F-Box Protein
- SEL10:
-
Suppressor and/or Enhancer of abnormal cell LINeage-12 (Lin-12)-10
- FBWX7:
-
F-Box and WD Repeat Domain containing 7
- SIRT-1:
-
Sirtuin-1
- CARM1:
-
Coactivator-Associated Arginine Methyltransferase1
- PRMT4:
-
Protein Arginine N-MethylTransferase 4
- CTBP:
-
C-Terminal Binding Protein
- CTIP:
-
CTBP Interacting Protein
- KYOT2/FHL1:
-
Four and a Half LIM domains 1
- NCoR:
-
Nuclear Receptor CoRepressor
- SMRT:
-
Silencing Mediator For Retinoid And Thyroid Hormone Receptors
- SHARP:
-
SMRT/HDAC1-Associated Repressor Protein
- SPEN:
-
SPlit ENds family transcriptional repressor
- LID:
-
Little Imaginal Disks
- KDM5A:
-
Lysine(K) Demethylase 5A
- CIR:
-
Corepressor Interacting with RBPJ
- SKIP:
-
Sloan-KetterIng-retroviral oncogene (SKI) -Interacting Protein
- L3MBTL3:
-
Lethal(3)Malignant Brain Tumor-Like Protein 3
- RITA1:
-
RBPJ Interacting and Tubulin Associated 1
- EBNA2:
-
Epstein-Barr Virus Nuclear Antigen 2
- NFAT:
-
Nuclear Factor of Activated T-cells
- NF-κB1:
-
Nuclear Factor κB1
- POFUT1:
-
Protein O-Fucosyltransferase 1
- Fringe:
-
Beta-1,3-N-Acetylglucosaminyltransferase
References
Arnett KL, Hass M, McArthur DG, Ilagan MX, Aster JC, Kopan R, Blacklow SC (2010) Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. Nat Struct Mol Biol 17(11):1312–1317. https://doi.org/10.1038/nsmb.1938
Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776 https://doi.org/10.1126/science.284.5415.770
Bailey AM, Posakony JW (1995) Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes Dev 9(21):2609–2622 https://doi.org/10.1101/gad.9.21.2609
Barolo S, Stone T, Bang AG, Posakony JW (2002) Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Genes Dev 16(15):1964–1976. https://doi.org/10.1101/gad.987402
Bertagna A, Toptygin D, Brand L, Barrick D (2008) The effects of conformational heterogeneity on the binding of the Notch intracellular domain to effector proteins: a case of biologically tuned disorder. Biochem Soc Trans 36(Pt 2):157–166. https://doi.org/10.1042/BST0360157
Borggrefe T, Oswald F (2009) The Notch signaling pathway: transcriptional regulation at Notch target genes. Cell Mol Life Sci 66(10):1631–1646 https://doi.org/10.1007/s00018-009-8668-7
Bozkulak EC, Weinmaster G (2009) Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling. Mol Cell Biol 29(21):5679–5695. https://doi.org/10.1128/mcb.00406-09
Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7(9):678–689. https://doi.org/10.1038/nrm2009
Bray SJ (2016) Notch signalling in context. Nat Rev Mol Cell Biol 17(11):722–735. https://doi.org/10.1038/nrm.2016.94
Brockmann B, Mastel H, Oswald F, Maier D (2014) Analysis of the interaction between human RITA and Drosophila Suppressor of Hairless. Hereditas 151(6):209–219. https://doi.org/10.1111/hrd2.00074
Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israel A (2000) A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 5(2):207–216 https://doi.org/10.1016/S1097-2765(00)80417-7
Bruckner K, Perez L, Clausen H, Cohen S (2000) Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406(6794):411–415. https://doi.org/10.1038/35019075
Castel D, Mourikis P, Bartels SJ, Brinkman AB, Tajbakhsh S, Stunnenberg HG (2013) Dynamic binding of RBPJ is determined by Notch signaling status. Genes Dev 27(9):1059–1071. https://doi.org/10.1101/gad.211912.112
Choi SH, Wales TE, Nam Y, O'Donovan DJ, Sliz P, Engen JR, Blacklow SC (2012) Conformational locking upon cooperative assembly of notch transcription complexes. Structure 20(2):340–349. https://doi.org/10.1016/j.str.2011.12.011
Collins KJ, Yuan Z, Kovall RA (2014) Structure and function of the CSL-KyoT2 corepressor complex: a negative regulator of Notch signaling. Structure 22(1):70–81. https://doi.org/10.1016/j.str.2013.10.010
Contreras AN, Yuan Z, Kovall RA (2015) Thermodynamic binding analysis of Notch transcription complexes from Drosophila melanogaster. Protein Sci Publ Protein Soc 24(5):812–822. https://doi.org/10.1002/pro.2652
Del Bianco C, Aster JC, Blacklow SC (2008) Mutational and energetic studies of Notch 1 transcription complexes. J Mol Biol 376(1):131–140 https://doi.org/10.1016/j.jmb.2007.11.061
Del Bianco C, Vedenko A, Choi SH, Berger MF, Shokri L, Bulyk ML, Blacklow SC (2010) Notch and MAML-1 complexation do not detectably alter the dna binding specificity of the transcription factor CSL. PLoS One 5(11):e15034. https://doi.org/10.1371/journal.pone.0015034
Dou S, Zeng X, Cortes P, Erdjument-Bromage H, Tempst P, Honjo T, Vales LD (1994) The recombination signal sequence-binding protein RBP-2N functions as a transcriptional repressor. Mol Cell Biol 14(5):3310–3319 https://doi.org/10.1128/MCB.14.5.3310
Friedmann DR, Kovall RA (2010) Thermodynamic and structural insights into CSL-DNA complexes. Protein Sci Publ Protein Soc 19(1):34–46. https://doi.org/10.1002/pro.280
Friedmann DR, Wilson JJ, Kovall RA (2008) RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. J Biol Chem 283(21):14781–14791. https://doi.org/10.1074/jbc.M709501200
Fryer CJ, White JB, Jones KA (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16(4):509–520. https://doi.org/10.1016/j.molcel.2004.10.014
Fuchs KP, Bommer G, Dumont E, Christoph B, Vidal M, Kremmer E, Kempkes B (2001) Mutational analysis of the J recombination signal sequence binding protein (RBPJ)/ Epstein-Barr virus nuclear antigen 2 (EBNA2) and RBP-J/Notch interaction. Eur J Biochem 268(17):4639–4646 https://doi.org/10.1046/j.1432-1327.2001.02387.x
Gordon WR, Zimmerman B, He L, Miles LJ, Huang J, Tiyanont K, McArthur DG, Aster JC, Perrimon N, Loparo JJ, Blacklow SC (2015) Mechanical Allostery: evidence for a force requirement in the proteolytic activation of Notch. Dev Cell 33(6):729–736. https://doi.org/10.1016/j.devcel.2015.05.004
Guarani V, Deflorian G, Franco CA, Kruger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M (2011) Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473(7346):234–238. https://doi.org/10.1038/nature09917
Hass MR, Liow HH, Chen X, Sharma A, Inoue YU, Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R (2016) SpDamID: marking DNA bound by protein complexes identifies Notch-dimer responsive enhancers. Mol Cell 64(1):213. https://doi.org/10.1016/j.molcel.2016.09.035
Hein K, Mittler G, Cizelsky W, Kuhl M, Ferrante F, Liefke R, Berger IM, Just S, Strang JE, Kestler HA, Oswald F, Borggrefe T (2015) Site-specific methylation of Notch1 controls the amplitude and duration of the Notch1 response. Sci Signal 8(369):ra30. https://doi.org/10.1126/scisignal.2005892
Hsieh JJ, Hayward SD (1995) Masking of the CBF1/RBPJ kappa transcriptional repression domain by Epstein-Barr virus EBNA2. Science 268(5210):560–563 https://doi.org/10.1126/science.7725102
Hsieh JJ, Zhou S, Chen L, Young DB, Hayward SD (1999) CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex. Proc Natl Acad Sci U S A 96(1):23–28 https://doi.org/10.1073/pnas.96.1.23
Hu B, Castillo E, Harewood L, Ostano P, Reymond A, Dummer R, Raffoul W, Hoetzenecker W, Hofbauer GF, Dotto GP (2012) Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. Cell 149(6):1207–1220. https://doi.org/10.1016/j.cell.2012.03.048
Johnson SE, Ilagan MX, Kopan R, Barrick D (2010) 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 285(9):6681–6692. https://doi.org/10.1074/jbc.M109.019968
Kadam S, Emerson BM (2003) Transcriptional specificity of human SWI/SNF BRG1 and BRM chromatin remodeling complexes. Mol Cell 11(2):377–389 https://doi.org/10.1016/S1097-2765(03)00034-0
Kao HY, Ordentlich P, Koyano-Nakagawa N, Tang Z, Downes M, Kintner CR, Evans RM, Kadesch T (1998) A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 12(15):2269–2277 https://doi.org/10.1101/gad.12.15.2269
Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137(2):216–233. https://doi.org/10.1016/j.cell.2009.03.045
Kovall RA, Blacklow SC (2010) Mechanistic insights into Notch receptor signaling from structural and biochemical studies. Curr Top Dev Biol 92:31–71. https://doi.org/10.1016/s0070-2153(10)92002-4
Kovall RA, Hendrickson WA (2004) Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. EMBO J 23(17):3441–3451. https://doi.org/10.1038/sj.emboj.7600349
Kovall RA, Gebelein B, Sprinzak D, Kopan R (2017) The canonical notch signaling pathway: structural and biochemical insights into shape, sugar, and force. Dev Cell 41(3):228–241. https://doi.org/10.1016/j.devcel.2017.04.001
Krejci A, Bray S (2007) Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers. Genes Dev 21(11):1322–1327 https://doi.org/10.1101/gad.424607
Kulic I, Robertson G, Chang L, Baker JH, Lockwood WW, Mok W, Fuller M, Fournier M, Wong N, Chou V, Robinson MD, Chun HJ, Gilks B, Kempkes B, Thomson TA, Hirst M, Minchinton AI, Lam WL, Jones S, Marra M, Karsan A (2015) Loss of the Notch effector RBPJ promotes tumorigenesis. J Exp Med 212(1):37–52. https://doi.org/10.1084/jem.20121192
Kuroda K, Han H, Tani S, Tanigaki K, Tun T, Furukawa T, Taniguchi Y, Kurooka H, Hamada Y, Toyokuni S, Honjo T (2003) Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 18(2):301–312 https://doi.org/10.1016/S1074-7613(03)00029-3
Kurooka H, Honjo T (2000) Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem 275(22):17211–17220. https://doi.org/10.1074/jbc.M000909200
Liefke R, Oswald F, Alvarado C, Ferres-Marco D, Mittler G, Rodriguez P, Dominguez M, Borggrefe T (2010) Histone demethylase KDM5A is an integral part of the core Notch- RBP-J repressor complex. Genes Dev 24(6):590–601 https://doi.org/10.1101/gad.563210
Logeat F, Bessia C, Brou C, LeBail O, Jarriault S, Seidah NG, Israel A (1998) The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci U S A 95(14):8108–8112 https://doi.org/10.1073/pnas.95.14.8108
Lubman OY, Ilagan MX, Kopan R, Barrick D (2007) Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch. J Mol Biol 365(3):577–589. https://doi.org/10.1016/j.jmb.2006.09.071
Maier D (2006) Hairless: the ignored antagonist of the Notch signalling pathway. Hereditas 143(2006):212–221. https://doi.org/10.1111/j.2007.0018-0661.01971.x
Maier D, Kurth P, Schulz A, Russell A, Yuan Z, Gruber K, Kovall RA, Preiss A (2011) Structural and functional analysis of the repressor complex in the Notch signaling pathway of Drosophila melanogaster. Mol Biol Cell 22(17):3242–3252 https://doi.org/10.1091/mbc.E11-05-0420
Meng X, Brodsky MH, Wolfe SA (2005) A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat Biotechnol 23(8):988–994 https://doi.org/10.1038/nbt1120
Moloney DJ, Panin VM, Johnston SH, Chen J, Shao L, Wilson R, Wang Y, Stanley P, Irvine KD, Haltiwanger RS, Vogt TF (2000) Fringe is a glycosyltransferase that modifies Notch. Nature 406(6794):369–375. https://doi.org/10.1038/35019000
Morel V, Lecourtois M, Massiani O, Maier D, Preiss A, Schweisguth F (2001) Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila. Curr Biol 11(10):789–792 https://doi.org/10.1016/S0960-9822(01)00224-X
Morgan TH (1917) The theory of the gene. Am Nat 51:513–544 https://doi.org/10.1086/279629
Moshkin YM, Kan TW, Goodfellow H, Bezstarosti K, Maeda RK, Pilyugin M, Karch F, Bray SJ, Demmers JA, Verrijzer CP (2009) Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Mol Cell 35(6):782–793. https://doi.org/10.1016/j.molcel.2009.07.020
Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, Pan DJ, Ray WJ, Kopan R (2000) A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol Cell 5(2):197–206 https://doi.org/10.1016/S1097-2765(00)80416-5
Nagel AC, Krejci A, Tenin G, Bravo-Patino A, Bray S, Maier D, Preiss A (2005) Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors. Mol Cell Biol 25(23):10433–10441. https://doi.org/10.1128/MCB.25.23.10433-10441.2005
Nam Y, Weng AP, Aster JC, Blacklow SC (2003) Structural requirements for assembly of the CSL.intracellular Notch1. Mastermind-like 1 transcriptional activation complex. J Biol Chem 278(23):21232–21239. https://doi.org/10.1074/jbc.M301567200
Nam Y, Sliz P, Song L, Aster JC, Blacklow SC (2006) Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell 124(5):973–983. https://doi.org/10.1016/j.cell.2005.12.037
Nam Y, Sliz P, Pear WS, Aster JC, Blacklow SC (2007) Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription. Proc Natl Acad Sci U S A 104(7):2103–2108. doi:0611092104 [pii]. https://doi.org/10.1073/pnas.0611092104
Neves A, English K, Priess JR (2007) Notch-GATA synergy promotes endoderm-specific expression of ref-1 in C. elegans. Development 134(24):4459–4468 https://doi.org/10.1242/dev.008680
Okajima T, Xu A, Irvine KD (2003) Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. J Biol Chem 278(43):42340–42345. https://doi.org/10.1074/jbc.M308687200
Olave I, Reinberg D, Vales LD (1998) The mammalian transcriptional repressor RBP (CBF1) targets TFIID and TFIIA to prevent activated transcription. Genes Dev 12(11):1621–1637 https://doi.org/10.1101/gad.12.11.1621
Oswald F, Tauber B, Dobner T, Bourteele S, Kostezka U, Adler G, Liptay S, Schmid RM (2001) p300 acts as a transcriptional coactivator for mammalian Notch-1. Mol Cell Biol 21(22):7761–7774. https://doi.org/10.1128/mcb.21.22.7761-7774.2001
Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knochel W, Liptay S, Schmid RM (2002) SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J 21(20):5417–5426 https://doi.org/10.1093/emboj/cdf549
Oswald F, Winkler M, Cao Y, Astrahantseff K, Bourteele S, Knochel W, Borggrefe T (2005) RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol Cell Biol 25(23):10379–10390 https://doi.org/10.1128/MCB.25.23.10379-10390.2005
Oswald F, Rodriguez P, Giaimo BD, Antonello ZA, Mira L, Mittler G, Thiel VN, Collins KJ, Tabaja N, Cizelsky W, Rothe M, Kuhl SJ, Kuhl M, Ferrante F, Hein K, Kovall RA, Dominguez M, Borggrefe T (2016) A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes. Nucleic Acids Res 44(10):4703–4720 https://doi.org/10.1093/nar/gkw105
Prevorovsky M, Atkinson SR, Ptackova M, McLean JR, Gould K, Folk P, Puta F, Bahler J (2011) N-termini of fungal CSL transcription factors are disordered, enriched in regulatory motifs and inhibit DNA binding in fission yeast. PLoS One 6(8):e23650. https://doi.org/10.1371/journal.pone.0023650
Qin H, Wang J, Liang Y, Taniguchi Y, Tanigaki K, Han H (2004) RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2. Nucleic Acids Res 32(4):1492–1501. https://doi.org/10.1093/nar/gkh295
Qin H, Du D, Zhu Y, Li J, Feng L, Liang Y, Han H (2005) The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2. FEBS Lett 579(5):1220–1226. https://doi.org/10.1016/j.febslet.2005.01.022
Rana NA, Haltiwanger RS (2011) Fringe benefits: functional and structural impacts of O-glycosylation on the extracellular domain of Notch receptors. Curr Opin Struct Biol 21(5):583–589. https://doi.org/10.1016/j.sbi.2011.08.008
Schroeter EH, Kisslinger JA, Kopan R (1998) Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393(6683):382–386. https://doi.org/10.1038/30756
Sherry KP, Johnson SE, Hatem CL, Majumdar A, Barrick D (2015) Effects of linker length and transient secondary structure elements in the intrinsically disordered notch RAM region on notch signaling. J Mol Biol 427(22):3587–3597. https://doi.org/10.1016/j.jmb.2015.09.001
Steinhauser K, Kloble P, Kreis NN, Ritter A, Friemel A, Roth S, Reichel JM, Michaelis J, Rieger MA, Louwen F, Oswald F, Yuan J (2016) Deficiency of RITA results in multiple mitotic defects by affecting microtubule dynamics. Oncogene. https://doi.org/10.1038/onc.2016.372
Struhl G, Adachi A (1998) Nuclear access and action of notch in vivo. Cell 93(4):649–660 https://doi.org/10.1016/S0092-8674(00)81193-9
Struhl G, Greenwald I (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398(6727):522–525. https://doi.org/10.1038/19091
Surendran K, Boyle S, Barak H, Kim M, Stomberski C, McCright B, Kopan R (2010) 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 337(2):386–395. https://doi.org/10.1016/j.ydbio.2009.11.017
Tabaja N, Yuan Z, Oswald F, Kovall RA (2017) Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes. J Biol Chem 292(25):10549–10563. https://doi.org/10.1074/jbc.M117.791707
Takeuchi H, Haltiwanger RS (2010) Role of glycosylation of Notch in development. Semin Cell Dev Biol 21(6):638–645. https://doi.org/10.1016/j.semcdb.2010.03.003
Takeuchi H, Haltiwanger RS (2014) Significance of glycosylation in Notch signaling. Biochem Biophys Res Commun 453(2):235–242. https://doi.org/10.1016/j.bbrc.2014.05.115
Tamura K, Taniguchi Y, Minoguchi S, Sakai T, Tun T, Furukawa T, Honjo T (1995) Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Curr Biol 5(12):1416–1423 https://doi.org/10.1016/S0960-9822(95)00279-X
Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T (1998) LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Mol Cell Biol 18(1):644–654 https://doi.org/10.1128/MCB.18.1.644
Torella R, Li J, Kinrade E, Cerda-Moya G, Contreras AN, Foy R, Stojnic R, Glen RC, Kovall RA, Adryan B, Bray SJ (2014) A combination of computational and experimental approaches identifies DNA sequence constraints associated with target site binding specificity of the transcription factor CSL. Nucleic Acids Res 42(16):10550–10563. https://doi.org/10.1093/nar/gku730
Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, Bessho Y, Kageyama R, Suda T, Nakayama KI (2004) Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 279(10):9417–9423. https://doi.org/10.1074/jbc.M312337200
Tun T, Hamaguchi Y, Matsunami N, Furukawa T, Honjo T, Kawaichi M (1994) Recognition sequence of a highly conserved DNA binding protein RBP-J kappa. Nucleic Acids Res 22(6):965–971
VanderWielen BD, Yuan Z, Friedmann DR, Kovall RA (2011) Transcriptional repression in the Notch pathway: thermodynamic characterization of CSL-MINT (Msx2-interacting nuclear target protein) complexes. J Biol Chem 286(17):14892–14902. https://doi.org/10.1074/jbc.M110.181156
Wacker SA, Alvarado C, von Wichert G, Knippschild U, Wiedenmann J, Clauss K, Nienhaus GU, Hameister H, Baumann B, Borggrefe T, Knochel W, Oswald F (2011) RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J. EMBO J 30(1):43–56 https://doi.org/10.1038/emboj.2010.289
Wallberg AE, Pedersen K, Lendahl U, Roeder RG (2002) p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Mol Cell Biol 22(22):7812–7819 https://doi.org/10.1128/MCB.22.22.7812-7819.2002
Weng AP, Nam Y, Wolfe MS, Pear WS, Griffin JD, Blacklow SC, Aster JC (2003) Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol 23(2):655–664 https://doi.org/10.1128/MCB.23.2.655-664.2003
Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S (1985) Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43(3 Pt 2):567–581
Wilson JJ, Kovall RA (2006) Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell 124(5):985–996. https://doi.org/10.1016/j.cell.2006.01.035
Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (2001) SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol 21(21):7403–7415. https://doi.org/10.1128/mcb.21.21.7403-7415.2001
Xu T, Park SS, Giaimo BD, Hall D, Ferrante F, Ho DM, Hori K, Anhezini L, Ertl I, Bartkuhn M, Zhang H, Milon E, Ha K, Conlon KP, Kuick R, Govindarajoo B, Zhang Y, Sun Y, Dou Y, Basrur V, Elenitoba-Johnson KS, Nesvizhskii AI, Ceron J, Lee CY, Borggrefe T, Kovall RA, Rual JF (2017) RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. EMBO J 36(21):3232–3249. https://doi.org/10.15252/embj.201796525
Yuan Z, Friedmann DR, VanderWielen BD, Collins KJ, Kovall RA (2012) Characterization of CSL (CBF-1, Su(H), Lag-1) mutants reveals differences in signaling mediated by Notch1 and Notch2. J Biol Chem 287(42):34904–34916. doi:M112.403287 [pii]. https://doi.org/10.1074/jbc.M112.403287
Yuan Z, Praxenthaler H, Tabaja N, Torella R, Preiss A, Maier D, Kovall RA (2016) Structure and function of the Su(H)-Hairless repressor complex, the major antagonist of notch signaling in Drosophila melanogaster. PLoS Biol 14(7):e1002509. https://doi.org/10.1371/journal.pbio.1002509
Zhou S, Hayward SD (2001) Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex. Mol Cell Biol 21(18):6222–6232 https://doi.org/10.1128/MCB.21.18.6222-6232.2001
Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD (2000) SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC to facilitate NotchIC function. Mol Cell Biol 20(7):2400–2410 https://doi.org/10.1128/MCB.20.7.2400-2410.2000
Zweifel ME, Leahy DJ, Hughson FM, Barrick D (2003) Structure and stability of the ankyrin domain of the Drosophila Notch receptor. Protein Sci Publ Protein Soc 12(11):2622–2632. https://doi.org/10.1110/ps.03279003
Acknowledgments
We want to thank Bernd Baumann for critical reading of the manuscript. Research in the F.O. laboratory is supported by the DFG (SFB1074/A3) and the BMBF (Federal Ministry of Education and Research, research nucleus SyStAR). Research in the R.A.K. laboratory is supported by the NIH (CA178974), NSF (MCB-1715822), and the Bankhead-Coley Cancer Research Program.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Oswald, F., Kovall, R.A. (2018). CSL-Associated Corepressor and Coactivator Complexes. In: Borggrefe, T., Giaimo, B. (eds) Molecular Mechanisms of Notch Signaling. Advances in Experimental Medicine and Biology, vol 1066. Springer, Cham. https://doi.org/10.1007/978-3-319-89512-3_14
Download citation
DOI: https://doi.org/10.1007/978-3-319-89512-3_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-89511-6
Online ISBN: 978-3-319-89512-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)