Notch signaling in leukemia

Annual Review of Pathology: Mechanisms of Disease

Volumn 3, Issue , 2008, Pages 587-613

  Aster, Jon C ^a   Pear, Warren S ^b   Blacklow, Stephen C ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Expression profiling; Mouse modeling; Regulated intramembranous proteolysis; Targeted therapy; Transcriptional activation

Indexed keywords

NOTCH1 RECEPTOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; CANCER GENETICS; GENE MUTATION; HUMAN; LEUKEMIA; LEUKEMOGENESIS; LYMPHOBLASTOMA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T CELL LEUKEMIA; T CELL LYMPHOMA;

ANIMALS; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LEUKEMIA; MICE; NEOPLASM PROTEINS; RECEPTOR, NOTCH1; SIGNAL TRANSDUCTION;

EID: 41749118698     PISSN: 15534006     EISSN: 15534014     Source Type: Book Series    
DOI: 10.1146/annurev.pathmechdis.3.121806.154300     Document Type: Review

References (145)

1. Bray SJ. 2006. Notch signalling: a simple pathway becomes complex. Nat. Rev. Mol. Cell. Biol. 7:678-89
2. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, et al. 1991. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649-61
3. Aster J, Pear W, Hasserjian R, Erba H, Davi F, et al. 1994. Functional analysis of the TAN-1 gene, a human homolog of Drosophila notch. Cold Spring Harb. Symp. Quant. Biol. 59:125-36
4. Das I, Craig C, Funahashi Y, Jung KM, Kim TW, et al. 2004. Notch oncoproteins depend on γ-secretase/presenilin activity for processing and function. J. Biol. Chem. 279:30771-80
5. Palomero T, Barnes KC, Real PJ, Bender JL, Sulis ML, et al. 2006. CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to γ-secretase inhibitors. Leukemia 20:1279-87
6. Pear WS, Aster JC, Scott ML, Hasserjian RP, Soffer B, et al. 1996. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp. Med. 183:2283-91
7. Bellavia D, Campese AF, Alesse E, Vacca A, Felli MP, et al. 2000. Constitutive activation of NF-κB and T-cell leukemia/lymphoma in Notch3 transgenic mice. EMBO J. 19:3337-48
8. Aster JC, Xu L, Karnell FG, Patriub V, Pui JC, Pear WS. 2000. Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1. Mol. Cell. Biol. 20:7505-15
9. Girard L, Hanna Z, Beaulieu N, Hoemann CD, Simard C, et al. 1996. Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev. 10:1930-44
10. Feldman BJ, Hampton T, Cleary ML. 2000. A carboxy-terminal deletion mutant of Notch1 accelerates lymphoid oncogenesis in E2A-PBX1 transgenic mice. Blood 96:1906-13
11. Allman D, Karnell FG, Punt JA, Bakkour S, Xu L, et al. 2001. Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells. J. Exp. Med. 194:99-106
12. Bellavia D, Campese AF, Checquolo S, Balestri A, Biondi A, et al. 2002. Combined expression of pTα and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc. Natl. Acad. Sci. USA 99:3788-93
13. Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, et al. 2003. Requirement for cyclin D3 in lymphocyte development and T cell leukemias. Cancer Cell 4:451-61
14. Pui JC, Allman D, Xu L, DeRocco S, Karnell FG, et al. 1999. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 11:299-308
15. Radtke F, Wilson A, Stark G, Bauer M, van Meerwijk J, et al. 1999. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10:547-58
16. Weng AP, Ferrando AA, Lee W, Morris JP, Silverman LB, et al. 2004. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269-71
17. Tamura K, Taniguchi Y, Minoguchi S, Sakai T, Tun T, et al. 1995. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J κ/SU(H). Curr. Biol. 5:1416-23
18. Lubman OY, Korolev SV, Kopan R. 2004. Anchoring notch genetics and biochemistry; structural analysis of the ankyrin domain sheds light on existing data. Mol. Cell 13:619-26
19. Kurooka H, Kuroda K, Honjo T. 1998. Roles of the ankyrin repeats and C-terminal region of the mouse notch1 intracellular region. Nucleic Acids Res. 26:5448-55
20. Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. 1997. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell 90:281-91
21. Logeat F, Bessia C, Brou C, LeBail O, Jarriault S, et al. 1998. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc. Natl. Acad. Sci. USA 95:8108-12
22. Rand MD, Grimm LM, Artavanis-Tsakonas S, Patriub V, Blacklow SC, et al. 2000. Calcium depletion dissociates and activates heterodimeric notch receptors. Mol. Cell. Biol. 20:1825-35
23. Sanchez-Irizarry C, Carpenter AC, Weng AP, Pear WS, Aster JC, Blacklow SC. 2004. Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeats. Mol. Cell. Biol. 24:9265-73
24. Brown MS, Ye J, Rawson RB, Goldstein JL. 2000. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100:391-98
25. Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S. 1991. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67:687-99
26. Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, et al. 2000. A ligand-induced extracellular cleavage regulates γ-secretase-like proteolytic activation of Notch1. Mol. Cell 5:197-206
27. Brou C, Logeat F, Gupta N, Bessia C, LeBail O, et al. 2000. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol. Cell 5:207-16
28. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, et al. 2000. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing. Nature 407:48-54
29. Chen F, Yu G, Arawaka S, Nishimura M, Kawarai T, et al. 2001. Nicastrin binds to membrane-tethered Notch. Nat. Cell Biol. 3:751-54
30. Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, et al. 2005. Nicastrin functions as a γ-secretase-substrate receptor. Cell 122:435-47
31. Schroeter EH, Kisslinger JA, Kopan R. 1998. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393:382-86
32. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, et al. 1999. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518-22
33. Struhl G, Greenwald I. 1999. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398:522-25
34. Itoh M, Kim CH, Palardy G, Oda T, Jiang YJ, et al. 2003. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev. Cell 4:67-82
35. Lai EC, Deblandre GA, Kintner C, Rubin GM. 2001. Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta. Dev. Cell 1:783-94
36. Deblandre GA, Lai EC, Kintner C. 2001. Xenopus neuralized is a ubiquitin ligase that interacts with XDelta1 and regulates Notch signaling. Dev. Cell 1:795-806
37. Yeh E, Dermer M, Commisso C, Zhou L, McGlade CJ, Boulianne GL. 2001. Neuralized functions as an E3 ubiquitin ligase during Drosophila development. Curr. Biol. 11:1675-79
38. Klueg KM, Muskavitch MA. 1999. Ligand-receptor interactions and trans-endocytosis of Delta, Serrate and Notch: members of the Notch signalling pathway in Drosophila. J. Cell Sci. 112:3289-97
39. Parks AL, Klueg KM, Stout JR, Muskavitch MA. 2000. Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 127:1373-85
40. Nichols JT, Miyamoto A, Olsen SL, D'Souza B, Yao C, Weinmaster G. 2007. DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur. J. Cell Biol. 176:445-58
41. Matsunami N, Hamaguchi Y, Yamamoto Y, Kuze K, Kangawa K, et al. 1989. A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif. Nature 342:934-37
42. Furukawa T, Maruyama S, Kawaichi M, Honjo T. 1992. The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development. Cell 69:1191-97
43. Schweisguth F, Posakony JW. 1992. Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates. Cell 69:1199-212
44. Fortini ME, Artavanis-Tsakonas S. 1994. The suppressor of hairless protein participates in notch receptor signaling. Cell 79:273-82
45. Christensen S, Kodoyianni V, Bosenberg M, Friedman L, Kimble J. 1996. lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development 122:1373-83
46. Petcherski AG, Kimble J. 2000. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 405:364-68
47. Petcherski AG, Kimble J. 2000. Mastermind is a putative activator for Notch. Curr. Biol. 10:R471-73
48. Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD. 2000. MAML1, a human homologue of Drosophila mastermind, is a transcriptional coactivator for NOTCH receptors. Nat. Genet. 26:484-89
49. 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. 365:577-89
50. 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 124:973-83
51. Wilson JJ, Kovall RA. 2006. Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell 124:985-96
52. Wu L, Sun T, Kobayashi K, Gao P, Griffin JD. 2002. Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol. Cell. Biol. 22:7688-700
53. 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. 22:7812-19
54. Fryer CJ, Lamar E, Turbachova I, Kintner C, Jones KA. 2002. Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev. 16:1397-411
55. Fryer CJ, White JB, Jones KA. 2004. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol. Cell 16:509-20
56. Bray S, Musisi H, Bienz M. 2005. Brc1 is required for Notch signaling and histone modification. Dev. Cell 8:279-86
57. Hon K, Fostier M, Ito M, Fuwa TJ, Go MJ, et al. 2004. Drosophila Deltex mediates Suppressor of Hairless-independent and late-endosomal activation of Notch signaling. Development 131:5527-37
58. Matsuno K, Go MJ, Sun X, Eastman DS, Artavanis-Tsakonas S. 1997. Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements. Development 124:4265-73
59. Weng AP, Nam Y, Wolfe MS, Pear WS, Griffin JD, et al. 2003. Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol. Cell. Biol. 23:655-64
60. Berry LW, Westlund B, Schedl T. 1997. Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development 124:925-36
61. Greenwald I, Seydoux G. 1990. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans. Nature 346:197-99
62. Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig WD, et al. 2006. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 108:1151-57
63. van Vlierberghe P, Meijerink JP, Lee C, Ferrando AA, Look AT, et al. 2006. A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia. Leukemia 20:1245-53
64. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, et al. 2002. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1:75-87
65. Asnafi V, Beldjord K, Boulanger E, Comba B, Le Tutour P, et al. 2003. Analysis of TCR, pTα, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood 101:2693-703
66. Rohn JL, Lauring AS, Linenberger ML, Overbaugh J. 1996. Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma. J. Virol. 70:8071-80
67. Palomero T, McKenna K, O'Neil J, Galinsky I, Stone R, et al. 2006. Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias. Leukemia 20:1963-66
68. Keeshan K, He Y, Wouters BJ, Shestova O, Xu L, et al. 2006. Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia. Cancer Cell 10:401-11
69. Malecki MJ, Sanchez-Irizarry C, Mitchell JL, Histen G, Xu ML, et al. 2006. Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes. Mol. Cell. Biol. 26:4642-51
70. Gordon WR, Vardar-Ulu D, Histen G, Sanchez-Irizarry C, Aster JC, Blacklow SC. 2007. Structural basis for autoinhibition of Notch. Nat. Struct. Mol. Biol. 14:295-300
71. Tsuji H, Ishii-Ohba H, Ukai H, Katsube T, Ogiu T. 2003. Radiation-induced deletions in the 5′ end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas. Carcinogenesis 24:1257-68
72. Chiang MY, Xu ML, Histen G, Shestova O, Roy M, et al. 2006. Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1. Mol. Cell. Biol. 26:6261-71
73. Welcker M, Orian A, Jin J, Grim JA, Harper JW, et al. 2004. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc. Natl. Acad. Sci. USA 101:9085-90
74. Welcker M, Orian A, Grim JA, Eisenman RN, Clurman BE. 2004. A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size. Curr. Biol. 14:1852-57
75. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, et al. 2004. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 23:2116-25
76. Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, et al. 2004. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J. Biol. Chem. 279:9417-23
77. Welcker M, Singer J, Loeb KR, Grim J, Bloecher A, et al. 2003. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol. Cell 12:381-92
78. O'Neil J, Grim J, Strack P, Rao S, Tibbits D, et al. 2007. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to g-secretase inhibitors. J. Exp. Med. 204:1813-24
79. Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T, et al. 2007. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J. Exp. Med. 204:1825-35
80. Malyukova A, Dohda, T, von der Lehr N, Akhondi S, Corcoran M, et al. 2007. The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res. 67:5611-15
81. Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A. 1995. Signalling downstream of activated mammalian Notch. Nature 377:355-58
82. 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. 9:2609-22
83. Nellesen DT, Lai EC, Posakony JW. 1999. Discrete enhancer elements mediate selective responsiveness of enhancer of split complex genes to common transcriptional activators. Dev. Biol. 213:33-53
84. Rebeiz M, Reeves NL, Posakony JW. 2002. SCORE: a computational approach to the identification of cis-regulatory modules and target genes in whole-genome sequence data. Site clustering over random expectation. Proc. Natl. Acad. Sci. USA 99:9888-93
85. Ehebauer MT, Chirgadze DY, Hayward P, Martinez Arias A, Blundell TL. 2005. High-resolution crystal structure of the human Notch 1 ankyrin domain. Biochem. J. 392:13-20
86. Roehl H, Bosenberg M, Blelloch R, Kimble J. 1996. Roles of the RAM and ANK domains in signaling by the C. elegans GLP-1 receptor. EMBO J. 15:7002-12
87. Zweifel ME, Barrick D. 2001. Studies of the ankyrin repeats of the Drosophila melanogaster Notch receptor. 2. Solution stability and cooperativity of unfolding. Biochemistry 40:14357-67
88. 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. 278:21232-39
89. 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. USA 104:2103-8
90. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, et al. 2006. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev. 20:2096-109
91. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, et al. 2006. NOTCH1 directly regelates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc. Natl. Acad. Sci. USA 103:18261-66
92. Lewis HD, Leveridge M, Strack PR, Haldon CD, O'Neil J, et al. 2007. Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling. Chem. Biol. 14:209-19
93. Chan S, Weng AP, Tibshirani R, Aster JC, Utz PJ. 2007. Notch signals positively regulate activity of the mTOR pathway in T cell acute lymphoblastic leukemia. Blood 110:278-86
94. O'Neil J, Calvo J, McKenna K, Krishnamoorthy V, Aster JC, et al. 2006. Activating Notch1 mutations in mouse models of T-ALL. Blood 107:781-85
95. Beverly LJ, Capobianco AJ. 2003. Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in Notch(IC)-induced T cell leukemogenesis. Cancer Cell 3:5 51-64
96. Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, et al. 2006. Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol. Cell. Biol. 26:8022-31
97. Maillard I, Weng AP, Carpenter AC, Rodriguez CG, Sai H, et al. 2004. Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 104:1696-702
98. Proweller A, Tu L, Lepore JJ, Cheng L, Lu MM, et al. 2006. Impaired notch signaling promotes de novo squamous cell carcinoma formation. Cancer Res. 66:7438-44
99. Sambandam A, Maillard I, Zediak VP, Xu L, Gerstein RM, et al. 2005. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat. Immunol. 6:663-70
100. Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, et al. 2006. The requirement for Notch signaling at the β-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J. Exp. Med. 203:2239-45
101. Fingar DC, Salama S, Tsou C, Harlow E, Blenis J. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16:1472-87
102. Zhang H, Stallock JP, Ng JC, Reinhard C, Neufeld TP. 2000. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14:2712-24
103. Fernandes J, Tavares MJ, Miele L, Cardoso AA, Classon M, Carlesso N. 2005. Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation. J. Exp. Med. 202:157-68
104. Kang-Decker N, Tong C, Boussouar F, Baker DJ, Xu W, et al. 2004. Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer Cell 5:177-89
105. Palomero T, Sulis M, Cortina M, Real PJ, Barnes K, et al. Mutational loss of PTEN induces an oncogene addiction switch and promotes resistance to NOTCH1 inhibition in T-cell leukemia. Nat. Med. 13:1203-10
106. θ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. Oncogene 24:992-1000
107. Domenga V, Fardoux P, Lacombe P, Monet M, Maciazek J, et al. 2004. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev. 18:2730-35
108. Radtke F, Wilson A, Mancini SJ, MacDonald HR. 2004. Notch regulation of lymphocyte development and function. Nat. Immunol. 5:247-53
109. Maillard I, Fang T, Pear WS. 2005. Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu. Rev. Immunol. 23:945-74
110. Maeda T, Merghoub T, Hobbs RM, Dong L, Maeda M et al. 2007. Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science 316:860-66
111. Maillard I, Shestova O, Pross SE, Xu L, Sai H, et al. Canonical Notch signaling is dispensable for the self-renewal of adult hematopoietic stem cells. Cell Stem Cell. Manuscript submitted
112. Xu Y, Davidson L, Alt FW, Baltimore D. 1996. Function of the pre-T-cell receptor α chain in T-cell development and allelic exclusion at the T-cell receptor β locus. Proc. Natl. Acad. Sci. USA 93:2169-73
113. Ciofani M, Schmitt TM, Ciofani A, Michie AM, Cuburu N, et al. 2004. Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation. J. Immunol. 172:5230-39
114. Taghon TN, David ES, Zuniga-Pflucker JC, Rothenberg EV. 2005. Delayed, asynchronous, and reversible T-lineage specification induced by Notch/Delta signaling. Genes Dev. 19:965-78
115. Dose M, Khan I, Guo Z, Kovalovsky D, Krueger A, et al. 2006. c-Myc mediates preTCR-induced proliferation but not developmental progression. Blood 108:2669-77
116. Ciofani M, Zuniga-Pflucker JC. 2005. Notch promotes survival of pre-T cells at the β-selection checkpoint by regulating cellular metabolism. Nat. Immunol. 6:881-88
117. Gao X, Pan D. 2001. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15:1383-92
118. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. 2002. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10:151-62
119. -/- mice by anti-CD3ε antibody treatment or with transgenes encoding activated Lck or tailless pTα. Immunity 6:703-14
120. Campese AF, Garbe AI, Zhang F, Grassi F, Screpanti I, von Boehmer H. 2006. Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling. Blood 108:305-10
121. Georgopoulos K, Bigby M, Wang JH, Molnar A, Wu P, et al. 1994. The Ikaros gene is required for the development of all lymphoid lineages. Cell 79:143-56
122. Yoshida T, Ng SY, Zuniga-Pflucker JC, Georgopoulos K. 2006. Early hematopoietic lineage restrictions directed by Ikaros. Nat. Immunol. 7:382-91
123. Winandy S, Wu L, Wang JH, Georgopoulos K. 1999. Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros. J. Exp. Med. 190:1039-48
124. Dumortier A, Jeannet R, Kirstetter P, Kleinmann E, Sellars M, et al. 2006. Notch activation is an early and critical event during T-cell leukemogenesis in Ikaros-deficient mice. Mol. Cell. Biol. 26:209-20
125. Lopez-Nieva P, Santos J, Fernandez-Piqueras J. 2004. Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in γ-radiation-induced mouse thymic lymphomas. Carcinogenesis 25:1299-304
126. Zhuang Y, Soriano P, Weintraub H. 1994. The helix-loop-helix gene E2A is required for B cell formation. Cell 79:875-84
127. Bain G, Engel I, Robanus Maandag EC, te Riele HP, Voland JR, et al. 1997. E2A deficiency leads to abnormalities in αβ T-cell development and to rapid development of T-cell lymphomas. Mol. Cell. Biol. 17:4782-91
128. Yan W, Young AZ, Soares VC, Kelley R, Benezra R, Zhuang Y. 1997. High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol. Cell. Biol. 17:7317-27
129. Reschly EJ, Spaulding C, Vilimas T, Graham WV, Brumbaugh RL, et al. 2006. Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms. Blood 107:4115-21
130. Nie L, Xu M, Vladimirova A, Sun XH. 2003. Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities. EMBO J. 22:5780-92
131. Talora C, Campese AF, Bellavia D, Pascucci M, Checquolo S, et al. 2003. Pre-TCR-triggered ERK signalling-dependent downregulation of E2A activity in Notch3-induced T-cell lymphoma. EMBO Rep. 4:1067-72
132. Huang Z, Nie L, Xu M, Sun XH. 2004. Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of ubiquitination. Mol. Cell. Biol. 24:8951-62
133. Ikawa T, Kawamoto H, Goldrath AW, Murre C. 2006. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J. Exp. Med. 203:1329-42
134. Vilimas T, Mascarenhas J, Palomero T, Mandal M, Buonamici S, et al. 2007. Targeting the NF-κB signaling pathway in Notch1-induced T-cell leukemia. Nat. Med. 13:70-77
135. Oswald F, Liptay S, Adler G, Schmid RM. 1998. NF-κB2 is a putative target gene of activated Notch-1 via RBP-Jκ. Mol. Cell. Biol. 18:2077-88
136. Cheng P, Zlobin A, Volgina V, Gottipati S, Osborne B, et al. 2001. Notch-1 regulates NF-κB activity in hemopoietic progenitor cells. J. Immunol. 167:4458-67
137. Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, et al. 2006. Notch1 augments NF-κB activity by facilitating its nuclear retention. EMBO J. 25:129-38
138. Anderson MK. 2006. At the crossroads: diverse roles of early thymocyte transcriptional regulators. Immunol. Rev. 209:191-211
139. Deftos ML, He YW, Ojala EW, Bevan MJ. 1998. Correlating notch signaling with thymocyte maturation. Immunity 9:777-86
140. Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, et al. 2004. Chronic treatment with the gamma-secretase inhibitor LY-411575 inhibits β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J. Biol. Chem. 279:12876-82
141. Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S. 2005. Notch signals control the fate of immature progenitor cells in the intestine. Nature 435:964-68
142. van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, et al. 2005. Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435:959-63
143. Lin YW, Nichols RA, Letterio JJ, Aplan PD. 2006. Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma. Blood 107:2540-43
144. Hoemann CD, Beaulieu N, Girard L, Rebai N, Jolicoeur P. 2000. Two distinct Notch1 mutant alleles are involved in the induction of T-cell leukemia in c-myc transgenic mice. Mol. Cell. Biol. 20:3831-42
145. Mantha S, Ward M, McCafferty J, Herron A, Palomero T, et al. 2007. Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice. Leuk. Res. 31:321-27