Notch regulation of bone development and remodeling and related skeletal disorders

Calcified Tissue International

Volumn 90, Issue 2, 2012, Pages 69-75

  Zanotti, Stefano ^a,b   Canalis, Ernesto ^a,b  

^a SAINT FRANCIS HOSPITAL AND MEDICAL CENTER   (United States)

^b UNIVERSITY OF CONNECTICUT SCHOOL OF MEDICINE   (United States)

Author keywords

Bone and cartilage development; Bone tumor; Bone turnover; Osteoblast; Osteoclast; Remodeling

Indexed keywords

INTERLEUKIN 6; JAGGED1; NOTCH RECEPTOR; NOTCH1 RECEPTOR; NOTCH2 RECEPTOR; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPONTIN; OSTEOPROTEGERIN; PRESENILIN 1; PRESENILIN 2; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR RUNX2;

ALAGILLE SYNDROME; BONE CANCER; BONE DENSITY; BONE DEVELOPMENT; BONE DISEASE; BONE REMODELING; BRACHYDACTYLY; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CHONDROGENESIS; FRACTURE; FRAMESHIFT MUTATION; GENE EXPRESSION REGULATION; GENE FREQUENCY; GENE OVEREXPRESSION; GENE PRODUCT; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; HAJDU CHENEY SYNDROME; HETEROZYGOSITY; HUMAN; JAG1 GENE; JARCHO LEVIN SYNDROME; MISSENSE MUTATION; NONHUMAN; OSTEOBLAST; OSTEOCLASTOGENESIS; OSTEOPENIA; OSTEOPOROSIS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN MOTIF; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TRANSGENE;

ANIMALS; BONE DEVELOPMENT; BONE DISEASES; BONE REMODELING; HUMANS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EID: 84857052943     PISSN: 0171967X     EISSN: 14320827     Source Type: Journal    
DOI: 10.1007/s00223-011-9541-x     Document Type: Review

References (66)

1. BR Olsen AM Reginato W Wang 2000 Bone development Annu Rev Cell Dev Biol 16 191 220 11031235 10.1146/annurev.cellbio.16.1.191 1:CAS:528:DC%2BD3MXpvFOk (Pubitemid 32037505)
2. E Canalis A Giustina JP Bilezikian 2007 Mechanisms of anabolic therapies for osteoporosis N Engl J Med 357 905 916 17761594 10.1056/NEJMra067395 1:CAS:528:DC%2BD2sXpvVylurk%3D (Pubitemid 47347324)
3. B D'Souza A Miyamoto G Weinmaster 2008 The many facets of notch ligands Oncogene 27 5148 5167 18758484 10.1038/onc.2008.229
4. R Kopan MX Ilagan 2009 The canonical notch signaling pathway: unfolding the activation mechanism Cell 137 216 233 19379690 10.1016/j.cell.2009.03.045 1:CAS:528:DC%2BD1MXmvVaiu7g%3D
5. ME Fortini 2009 Notch signaling: the core pathway and its posttranslational regulation Dev Cell 16 633 647 19460341 10.1016/j.devcel.2009. 03.010 1:CAS:528:DC%2BD1MXps1yms7c%3D
6. T Iso L Kedes Y Hamamori 2003 HES and HERP families: multiple effectors of the notch signaling pathway J Cell Physiol 194 237 255 12548545 10.1002/jcp.10208 1:CAS:528:DC%2BD3sXhtFKiurs%3D (Pubitemid 36176887)
7. P Heitzler 2010 Biodiversity and noncanonical notch signaling Curr Top Dev Biol 92 457 481 20816404 10.1016/S0070-2153(10)92014-0 1:CAS:528: DC%2BC3cXht12jtLjK
8. S Bai R Kopan W Zou MJ Hilton CT Ong F Long FP Ross SL Teitelbaum 2008 NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells J Biol Chem 283 6509 6518 18156632 10.1074/jbc.M707000200 1:CAS:528:DC%2BD1cXisFOkt74%3D
9. Y Dong AM Jesse A Kohn LM Gunnell T Honjo MJ Zuscik RJ O'Keefe MJ Hilton 2010 RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development Development 137 1461 1471 20335360 10.1242/dev.042911 1:CAS:528:DC%2BC3cXnt1Gmu7o%3D
10. J Tao S Chen T Yang B Dawson E Munivez T Bertin B Lee 2010 Osteosclerosis owing to Notch gain of function is solely Rbpj-dependent J Bone Miner Res 25 2175 2183 20499347 10.1002/jbmr.115 1:CAS:528:DC%2BC3cXhtlaktb3J
11. B McCright J Lozier T Gridley 2006 Generation of new Notch2 mutant alleles Genesis 44 29 33 16397869 10.1002/gene.20181 1:CAS:528: DC%2BD28XhvFGmsbo%3D (Pubitemid 43222208)
12. PJ Swiatek CE Lindsell FF del Amo G Weinmaster T Gridley 1994 Notch1 is essential for postimplantation development in mice Genes Dev 8 707 719 7926761 10.1101/gad.8.6.707 1:CAS:528:DyaK2cXjtF2qurg%3D (Pubitemid 24116765)
13. D Bellavia S Checquolo AF Campese MP Felli A Gulino I Screpanti 2008 Notch3: from subtle structural differences to functional diversity Oncogene 27 5092 5098 18758477 10.1038/onc.2008.230 1:CAS:528:DC%2BD1cXhtVGgtLfJ
14. M Monet V Domenga B Lemaire C Souilhol F Langa C Babinet T Gridley E Tournier-Lasserve M Cohen-Tannoudji A Joutel 2007 The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo Hum Mol Genet 16 982 992 17331978 10.1093/hmg/ddm042 1:CAS:528:DC%2BD2sXmsVWnt7s%3D (Pubitemid 47062741)
15. LT Krebs Y Xue CR Norton JR Shutter M Maguire JP Sundberg D Gallahan V Closson J Kitajewski R Callahan GH Smith KL Stark T Gridley 2000 Notch signaling is essential for vascular morphogenesis in mice Genes Dev 14 1343 1352 10837027 1:CAS:528:DC%2BD3cXjvFOgsbg%3D (Pubitemid 30397078)
16. M Logan JF Martin A Nagy C Lobe EN Olson CJ Tabin 2002 Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer Genesis 33 77 80 12112875 10.1002/gene.10092 1:CAS:528:DC%2BD38XltlOrsL0%3D (Pubitemid 34651279)
17. S Zanotti E Canalis 2010 Notch and the skeleton Mol Cell Biol 30 886 896 19995916 10.1128/MCB.01285-09 1:CAS:528:DC%2BC3cXisVequro%3D
18. MJ Hilton X Tu X Wu S Bai H Zhao T Kobayashi HM Kronenberg SL Teitelbaum FP Ross R Kopan F Long 2008 Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation Nat Med 14 306 314 18297083 10.1038/nm1716 1:CAS:528:DC%2BD1cXivFOrtL8%3D (Pubitemid 351347911)
19. TJ Mead KE Yutzey 2009 Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development Proc Natl Acad Sci USA 106 14420 14425 19590010 10.1073/pnas. 0902306106 1:CAS:528:DC%2BD1MXhtFaiu73L
20. S Zanotti A Smerdel-Ramoya E Canalis 2011 Hairy and enhancer of split (HES)1 is a determinant of bone mass J Biol Chem 286 2648 2657 21084301 10.1074/jbc.M110.183038 1:CAS:528:DC%2BC3MXosVansQ%3D%3D
21. E Canalis 2005 The fate of circulating osteoblasts N Engl J Med 352 2014 2016 15888703 10.1056/NEJMe058080 1:CAS:528:DC%2BD2MXjvFyrtbo%3D (Pubitemid 40638373)
22. S Zanotti A Smerdel-Ramoya L Stadmeyer D Durant F Radtke E Canalis 2008 Notch inhibits osteoblast differentiation and causes osteopenia Endocrinology 149 3890 3899 18420737 10.1210/en.2008-0140 1:CAS:528:DC%2BD1cXptlamsbg%3D
23. F Engin Z Yao T Yang G Zhou T Bertin MM Jiang Y Chen L Wang H Zheng RE Sutton BF Boyce B Lee 2008 Dimorphic effects of Notch signaling in bone homeostasis Nat Med 14 299 305 18297084 10.1038/nm1712 1:CAS:528: DC%2BD1cXivFOrtL0%3D (Pubitemid 351347909)
24. I Kalajzic Z Kalajzic M Kaliterna G Gronowicz SH Clark AC Lichtler D Rowe 2002 Use of type I collagen green fluorescent protein transgenes to identify subpopulations of cells at different stages of the osteoblast lineage J Bone Miner Res 17 15 25 11771662 10.1359/jbmr.2002.17.1.15 1:CAS:528: DC%2BD38XktFyisw%3D%3D (Pubitemid 33150992)
25. V Deregowski E Gazzerro L Priest S Rydziel E Canalis 2006 Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling J Biol Chem 281 6203 6210 16407293 10.1074/jbc.M508370200 1:CAS:528:DC%2BD28XhvFOhtbk%3D (Pubitemid 43847550)
26. S Zanotti A Smerdel-Ramoya E Canalis 2011 Reciprocal regulation of notch and nuclear factor of activated T-cells (NFAT)c1 transactivation in osteoblasts J Biol Chem 286 4576 4588 21131365 10.1074/jbc.M110.161893 1:CAS:528: DC%2BC3MXhsFGltbo%3D
27. D Sitara AO Aliprantis 2010 Transcriptional regulation of bone and joint remodeling by NFAT Immunol Rev 233 286 300 20193006 10.1111/j.0105-2896.2009. 00849.x 1:CAS:528:DC%2BC3cXjslaqsrg%3D
28. Y Zhang JB Lian JL Stein AJ van Wijnen GS Stein 2009 The Notch-responsive transcription factor Hes-1 attenuates osteocalcin promoter activity in osteoblastic cells J Cell Biochem 108 651 659 19670267 10.1002/jcb.22299 1:CAS:528:DC%2BD1MXhtFyntLfM
29. JS Lee DM Thomas G Gutierrez SA Carty S Yanagawa PW Hinds 2006 HES1 cooperates with pRb to activate RUNX2-dependent transcription J Bone Miner Res 21 921 933 16753023 10.1359/jbmr.060303 1:CAS:528:DC%2BD28XlvVamu78%3D (Pubitemid 43787999)
30. KW McLarren R Lo D Grbavec K Thirunavukkarasu G Karsenty S Stifani 2000 The mammalian basic helix loop helix protein HES-1 binds to and modulates the transactivating function of the runt-related factor Cbfa1 J Biol Chem 275 530 538 10617648 10.1074/jbc.275.1.530 1:CAS:528:DC%2BD3cXjvVKhtA%3D%3D (Pubitemid 30039015)
31. Q Shen S Christakos 2005 The vitamin D receptor, Runx2, and the Notch signaling pathway cooperate in the transcriptional regulation of osteopontin J Biol Chem 280 40589 40598 16195230 10.1074/jbc.M504166200 1:CAS:528: DC%2BD2MXht1OqtrbJ (Pubitemid 41780549)
32. R Salie M Kneissel M Vukevic N Zamurovic I Kramer G Evans N Gerwin M Mueller B Kinzel M Susa 2010 Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and chondrocyte hypertrophy in bone Bone 46 680 694 19857617 10.1016/j.bone.2009.10.022 1:CAS:528:DC%2BC3cXitV2gs70%3D
33. Tu X, Lim K, Ganss K, Surendran R, Kopan R, Gessler M, Long F (2009) Notch inhibits early stages of osteoblastogenesis through RBP-Jk and hey proteins. J Bone Miner Res 24(Suppl 1). http://www.asbmr.org/Meetings/ AnnualMeeting/AbstractDetail.aspx?aid=3796349f-2835-4777-8547-1d873506308f
34. SL Teitelbaum 2007 Osteoclasts: What do they do and how do they do it? Am J Pathol 170 427 435 17255310 10.2353/ajpath.2007.060834 1:CAS:528: DC%2BD2sXitlOls74%3D (Pubitemid 47339379)
35. T Yamada H Yamazaki T Yamane M Yoshino H Okuyama M Tsuneto T Kurino S Hayashi S Sakano 2003 Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells Blood 101 2227 2234 12411305 10.1182/blood-2002-06-1740 1:CAS:528:DC%2BD3sXit1egsLc%3D (Pubitemid 36302062)
36. H Fukushima A Nakao F Okamoto M Shin H Kajiya S Sakano A Bigas E Jimi K Okabe 2008 The association of Notch2 and NF-kappaB accelerates RANKL-induced osteoclastogenesis Mol Cell Biol 28 6402 6412 18710934 10.1128/MCB.00299-08 1:CAS:528:DC%2BD1cXht1CitL7M
37. N Sethi X Dai CG Winter Y Kang 2011 Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells Cancer Cell 19 192 205 21295524 10.1016/j.ccr.2010.12.022 1:CAS:528:DC%2BC3MXhvFeksbo%3D
38. J Tian L Ling M Shboul H Lee B O'Connor B Merriman SF Nelson S Cool OH Ababneh A Al-Hadidy A Masri H Hamamy B Reversade 2010 Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling Am J Hum Genet 87 768 778 21129727 10.1016/j.ajhg.2010.11.005 1:CAS:528:DC%2BC3cXhsFags7nL
39. R Jiang Y Lan HD Chapman C Shawber CR Norton DV Serreze G Weinmaster T Gridley 1998 Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice Genes Dev 12 1046 1057 9531541 10.1101/gad.12.7.1046 1:CAS:528:DyaK1cXisl2gtLo%3D (Pubitemid 28204610)
40. A Sidow MS Bulotsky AW Kerrebrock RT Bronson MJ Daly MP Reeve TL Hawkins BW Birren R Jaenisch ES Lander 1997 Serrate2 is disrupted in the mouse limb-development mutant syndactylism Nature 389 722 725 9338782 10.1038/39587 1:CAS:528:DyaK2sXmvVSgs7c%3D (Pubitemid 27458957)
41. T Gridley 2003 Notch signaling and inherited disease syndromes Hum Mol Genet 12 R9 R13 12668592 10.1093/hmg/ddg052 1:CAS:528:DC%2BD3sXjs1Oltb0%3D
42. ID Krantz DA Piccoli NB Spinner 1999 Clinical and molecular genetics of alagille syndrome Curr Opin Pediatr 11 558 564 10590916 10.1097/00008480- 199912000-00015 1:STN:280:DC%2BD3c%2FlvVCgtQ%3D%3D
43. R McDaniell DM Warthen PA Sanchez-Lara A Pai ID Krantz DA Piccoli NB Spinner 2006 NOTCH2 mutations cause alagille syndrome, a heterogeneous disorder of the notch signaling pathway Am J Hum Genet 79 169 173 16773578 10.1086/505332 1:CAS:528:DC%2BD28Xmt1entL0%3D (Pubitemid 43927389)
44. B McCright J Lozier T Gridley 2002 A mouse model of alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency Development 129 1075 1082 11861489 1:CAS:528:DC%2BD38XitFygt7w%3D (Pubitemid 34874130)
45. PD Turnpenny B Alman AS Cornier PF Giampietro A Offiah O Tassy O Pourquie K Kusumi S Dunwoodie 2007 Abnormal vertebral segmentation and the notch signaling pathway in man Dev Dyn 236 1456 1474 17497699 10.1002/dvdy.21182 1:CAS:528:DC%2BD2sXnvFOhsb8%3D (Pubitemid 46932351)
46. SL Dunwoodie M Clements DB Sparrow X Sa RA Conlon RS Beddington 2002 Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm Development 129 1795 1806 11923214 1:CAS:528: DC%2BD38Xjt1eitL8%3D (Pubitemid 34874195)
47. K Kusumi ES Sun AW Kerrebrock RT Bronson DC Chi MS Bulotsky JB Spencer BW Birren WN Frankel ES Lander 1998 The mouse pudgy mutation disrupts delta homologue Dll3 and initiation of early somite boundaries Nat Genet 19 274 278 9662403 10.1038/961 1:CAS:528:DyaK1cXls1SnsLg%3D (Pubitemid 28309342)
48. Y Saga N Hata H Koseki MM Taketo 1997 Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation Genes Dev 11 1827 1839 9242490 10.1101/gad.11.14.1827 1:CAS:528:DyaK2sXkslKlsLw%3D (Pubitemid 27315212)
49. AS Cornier K Staehling-Hampton KM Delventhal Y Saga JF Caubet N Sasaki S Ellard E Young N Ramirez SE Carlo J Torres JB Emans PD Turnpenny O Pourquie 2008 Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome Am J Hum Genet 82 1334 1341 18485326 10.1016/j.ajhg.2008.04.014 1:CAS:528:DC%2BD1cXntlWqs7w%3D
50. NV Whittock DB Sparrow MA Wouters D Sillence S Ellard SL Dunwoodie PD Turnpenny 2004 Mutated MESP2 causes spondylocostal dysostosis in humans Am J Hum Genet 74 1249 1254 15122512 10.1086/421053 1:CAS:528:DC%2BD2cXks1Cqsrg%3D (Pubitemid 38669323)
51. P Stanley 2007 Regulation of Notch signaling by glycosylation Curr Opin Struct Biol 17 530 535 17964136 10.1016/j.sbi.2007.09.007 1:CAS:528: DC%2BD2sXht1KktbfN (Pubitemid 350019017)
52. SL Dunwoodie 2009 Mutation of the fucose-specific beta 1,3N-acetylglucosaminyltransferase LFNG results in abnormal formation of the spine Biochim Biophys Acta 1792 100 111 19061953 1:CAS:528:DC%2BD1MXhtFelsbw%3D
53. DB Sparrow G Chapman MA Wouters NV Whittock S Ellard D Fatkin PD Turnpenny K Kusumi D Sillence SL Dunwoodie 2006 Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype Am J Hum Genet 78 28 37 16385447 10.1086/498879 1:CAS:528: DC%2BD28XhslKktw%3D%3D (Pubitemid 41833157)
54. Y Bessho R Sakata S Komatsu K Shiota S Yamada R Kageyama 2001 Dynamic expression and essential functions of Hes7 in somite segmentation Genes Dev 15 2642 2647 11641270 10.1101/gad.930601 1:CAS:528:DC%2BD3MXnvVWksLg%3D (Pubitemid 32988874)
55. DB Sparrow E Guillen-Navarro D Fatkin SL Dunwoodie 2008 Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis Hum Mol Genet 17 3761 3766 18775957 10.1093/hmg/ddn272 1:CAS:528:DC%2BD1cXhtlGis77O
56. DB Sparrow D Sillence MA Wouters PD Turnpenny SL Dunwoodie 2010 Two novel missense mutations in Hairy-and-Enhancer-of-Split-7 in a family with spondylocostal dysostosis Eur J Hum Genet 18 674 679 20087400 10.1038/ejhg.2009.241 1:CAS:528:DC%2BC3cXmt1OjsLw%3D
57. B Isidor P Lindenbaum O Pichon S Bezieau C Dina S Jacquemont D Martin-Coignard C Thauvin-Robinet MM Le JL Mandel A David L Faivre V Cormier-Daire R Redon CC Le 2011 Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis Nat Genet 43 306 308 21378989 10.1038/ng.778 1:CAS:528:DC%2BC3MXivVSnsLg%3D
58. MA Simpson MD Irving E Asilmaz MJ Gray D Dafou FV Elmslie S Mansour SE Holder CE Brain BK Burton KH Kim RM Pauli S Aftimos H Stewart CA Kim M Holder-Espinasse SP Robertson WM Drake RC Trembath 2011 Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss Nat Genet 43 303 305 21378985 10.1038/ng.779 1:CAS:528:DC%2BC3MXivVSnt70%3D
59. AW Kung SM Xiao S Cherny GH Li Y Gao G Tso KS Lau KD Luk JM Liu B Cui MJ Zhang ZL Zhang JW He H Yue WB Xia LM Luo SL He DP Kiel D Karasik YH Hsu LA Cupples S Demissie U Styrkarsdottir BV Halldorsson G Sigurdsson U Thorsteinsdottir K Stefansson JB Richards G Zhai N Soranzo A Valdes TD Spector PC Sham 2010 Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies Am J Hum Genet 86 229 239 20096396 10.1016/j.ajhg.2009.12.014 1:CAS:528: DC%2BC3cXlt1Kmu70%3D
60. F Radtke N Fasnacht HR MacDonald 2010 Notch signaling in the immune system Immunity 32 14 27 20152168 10.1016/j.immuni.2010.01.004 1:CAS:528:DC%2BC3cXkvV2js7s%3D
61. KG Leong A Karsan 2006 Recent insights into the role of Notch signaling in tumorigenesis Blood 107 2223 2233 16291593 10.1182/blood-2005-08-3329 1:CAS:528:DC%2BD28XisFOjt7s%3D (Pubitemid 43345539)
62. F Engin T Bertin O Ma MM Jiang L Wang RE Sutton LA Donehower B Lee 2009 Notch signaling contributes to the pathogenesis of human osteosarcomas Hum Mol Genet 18 1464 1470 19228774 10.1093/hmg/ddp057 1:CAS:528:DC%2BD1MXktV2hurY%3D
63. P Zhang Y Yang PA Zweidler-McKay DP Hughes 2008 Critical role of notch signaling in osteosarcoma invasion and metastasis Clin Cancer Res 14 2962 2969 18483362 10.1158/1078-0432.CCR-07-1992 1:CAS:528:DC%2BD1cXmtVCmtLw%3D
64. Z Zhang H Wang S Ikeda F Fahey D Bielenberg P Smits PV Hauschka 2010 Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis Am J Pathol 177 1459 1469 20651241 10.2353/ajpath.2010.090476 1:CAS:528:DC%2BC3cXht1KmsbrM
65. SW Ryeom 2011 The cautionary tale of side effects of chronic Notch1 inhibition J Clin Invest 121 508 509 21266769 10.1172/JCI45976 1:CAS:528:DC%2BC3MXhsl2rur8%3D
66. RE Moellering M Cornejo TN Davis BC Del JC Aster SC Blacklow AL Kung DG Gilliland GL Verdine JE Bradner 2009 Direct inhibition of the NOTCH transcription factor complex Nature 462 182 188 19907488 10.1038/nature08543 1:CAS:528:DC%2BD1MXhsVSjsr3F