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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1696-1702. Prepublished online as a Blood First Edition Paper on June 8, 2004; DOI 10.1182/blood-2004-02-0514. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0514v1 104/6/1696    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maillard, I. Articles by Pear, W. S. Search for Related Content PubMed PubMed Citation Articles by Maillard, I. Articles by Pear, W. S. Related Collections Hematopoiesis and Stem Cells Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Mastermind critically regulates Notch-mediated lymphoid cell fate decisions Ivan Maillard, Andrew P. Weng, Andrea C. Carpenter, Carlos G. Rodriguez, Hong Sai, Lanwei Xu, David Allman, Jon C. Aster, and Warren S. Pear From the Division of Hematology-Oncology, Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Institute for Medicine & Engineering, University of Pennsylvania, Philadelphia; and the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. During lymphoid development, Notch1 plays a critical role in the T-cell/B-cell lineage decision, while Notch2 is essential for marginal zone B-cell (MZB) development. Notch pathway activation induces translocation of intracellular Notch (ICN) to the nucleus, where it interacts with the transcription factor CSL (CBF1/RBP-Jk, Suppressor of Hairless, Lag-1). In vitro, ICN binds Mastermind-like proteins, which act as potent Notch coactivators. Three MAML family members (MAML1-3) have been identified in mammals, but their importance in vivo is unknown. To investigate the function of MAMLs in hematopoietic development, we introduced a dominant negative (DN) mutant of MAML1, capable of inhibiting Notch1-4, in murine hematopoietic stem cells. DNMAML1 resulted in early inhibition of T-cell development and the appearance of intrathymic B cells, phenotypes consistent with Notch1 inhibition. The T-cell differentiation block was as profound as that produced by enforced expression of the Notch modulator Deltex1. In DNMAML1-transduced spleen cells, a dramatic decrease in MZB cells was present, consistent with Notch2 inhibition. In contrast, Deltex1 did not decrease MZB cell numbers. These results suggest a critical role for MAMLs during Notch-mediated cell fate decisions in vivo and indicate that DNMAML1, but not Deltex1, can be used to interfere with the function of multiple Notch family members. (Blood. 2004;104:1696-1702) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A mastermind revealed Shiv Pillai Blood 2004 104: 1593. [Full Text] [PDF] This article has been cited by other articles: Y. Yashiro-Ohtani, Y. He, T. Ohtani, M. E. Jones, O. Shestova, L. Xu, T. C. Fang, M. Y. Chiang, A. M. Intlekofer, S. C. Blacklow, et al. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A Genes & Dev., July 15, 2009; 23(14): 1665 - 1676. [Abstract] [Full Text] [PDF] S.-O. Yoon, X. Zhang, P. Berner, B. Blom, and Y. S. Choi Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J. Immunol., July 1, 2009; 183(1): 352 - 358. [Abstract] [Full Text] [PDF] H. Kohlhof, F. Hampel, R. Hoffmann, H. Burtscher, U. H. Weidle, M. Holzel, D. Eick, U. Zimber-Strobl, and L. J. Strobl Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells Blood, May 28, 2009; 113(22): 5506 - 5515. [Abstract] [Full Text] [PDF] T. Taghon, I. Van de Walle, G. De Smet, M. De Smedt, G. Leclercq, B. Vandekerckhove, and J. Plum Notch signaling is required for proliferation but not for differentiation at a well-defined {beta}-selection checkpoint during human T-cell development Blood, April 2, 2009; 113(14): 3254 - 3263. [Abstract] [Full Text] [PDF] X. Li, F. Gounari, A. Protopopov, K. Khazaie, and H. von Boehmer Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1 J. Exp. Med., November 24, 2008; 205(12): 2851 - 2861. [Abstract] [Full Text] [PDF] D.-M. Shin, D. J. Shaffer, H. Wang, D. C. Roopenian, and H. C. Morse III NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas Cancer Res., November 15, 2008; 68(22): 9202 - 9211. [Abstract] [Full Text] [PDF] S. Chari and S. Winandy Ikaros Regulates Notch Target Gene Expression in Developing Thymocytes J. Immunol., November 1, 2008; 181(9): 6265 - 6274. [Abstract] [Full Text] [PDF] R. Song, Y.-W. Kim, B.-K. Koo, H.-W. Jeong, M.-J. Yoon, K.-J. Yoon, D.-J. Jun, S.-K. Im, J. Shin, M.-P. Kong, et al. Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B cell development J. Exp. Med., October 27, 2008; 205(11): 2525 - 2536. [Abstract] [Full Text] [PDF] K. Niessen and A. Karsan Notch Signaling in Cardiac Development Circ. Res., May 23, 2008; 102(10): 1169 - 1181. [Abstract] [Full Text] [PDF] F. A. High, M. M. Lu, W. S. Pear, K. M. Loomes, K. H. Kaestner, and J. A. Epstein Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development PNAS, February 12, 2008; 105(6): 1955 - 1959. [Abstract] [Full Text] [PDF] J. J. Breunig, J. Silbereis, F. M. Vaccarino, N. Sestan, and P. Rakic Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus PNAS, December 18, 2007; 104(51): 20558 - 20563. [Abstract] [Full Text] [PDF] L. Wu, I. Maillard, M. Nakamura, W. S. Pear, and J. D. Griffin The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development Blood, November 15, 2007; 110(10): 3618 - 3623. [Abstract] [Full Text] [PDF] A. Proweller, A. C. Wright, D. Horng, L. Cheng, M. M. Lu, J. J. Lepore, W. S. Pear, and M. S. Parmacek Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature PNAS, October 9, 2007; 104(41): 16275 - 16280. [Abstract] [Full Text] [PDF] C. Spaulding, E. J. Reschly, D. E. Zagort, Y. Yashiro-Ohtani, L. J. Beverly, A. Capobianco, W. S. Pear, and B. L. Kee Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas Blood, October 1, 2007; 110(7): 2650 - 2658. [Abstract] [Full Text] [PDF] M. De Smedt, T. Taghon, I. Van de Walle, G. De Smet, G. Leclercq, and J. Plum Notch signaling induces cytoplasmic CD3{epsilon} expression in human differentiating NK cells Blood, October 1, 2007; 110(7): 2696 - 2703. [Abstract] [Full Text] [PDF] M. A. Santos, L. M. Sarmento, M. Rebelo, A. A. Doce, I. Maillard, A. Dumortier, H. Neves, F. Radtke, W. S. Pear, L. Parreira, et al. Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells PNAS, September 25, 2007; 104(39): 15454 - 15459. [Abstract] [Full Text] [PDF] M. L. Caton, M. R. Smith-Raska, and B. Reizis Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen J. Exp. Med., July 9, 2007; 204(7): 1653 - 1664. [Abstract] [Full Text] [PDF] S. T. Moran, A. Cariappa, H. Liu, B. Muir, D. Sgroi, C. Boboila, and S. Pillai Synergism between NF-{kappa}B1/p50 and Notch2 during the Development of Marginal Zone B Lymphocytes J. Immunol., July 1, 2007; 179(1): 195 - 200. [Abstract] [Full Text] [PDF] T. Oyama, K. Harigaya, A. Muradil, K. Hozumi, S. Habu, H. Oguro, A. Iwama, K. Matsuno, R. Sakamoto, M. Sato, et al. Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo PNAS, June 5, 2007; 104(23): 9764 - 9769. [Abstract] [Full Text] [PDF] X. Ma, M. J. Renda, L. Wang, E.-c. Cheng, C. Niu, S. W. Morris, A. S. Chi, and D. S. Krause Rbm15 Modulates Notch-Induced Transcriptional Activation and Affects Myeloid Differentiation Mol. Cell. Biol., April 15, 2007; 27(8): 3056 - 3064. [Abstract] [Full Text] [PDF] M. Thomas, M. Calamito, B. Srivastava, I. Maillard, W. S. Pear, and D. Allman Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B-cell activation Blood, April 15, 2007; 109(8): 3342 - 3350. [Abstract] [Full Text] [PDF] K. Lefort, A. Mandinova, P. Ostano, V. Kolev, V. Calpini, I. Kolfschoten, V. Devgan, J. Lieb, W. Raffoul, D. Hohl, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCK{alpha} kinases Genes & Dev., March 1, 2007; 21(5): 562 - 577. [Abstract] [Full Text] [PDF] S. M. Lehar and M. J. Bevan T Cells Develop Normally in the Absence of both Deltex1 and Deltex2 Mol. Cell. Biol., October 15, 2006; 26(20): 7358 - 7371. [Abstract] [Full Text] [PDF] I. Maillard, L. Tu, A. Sambandam, Y. Yashiro-Ohtani, J. Millholland, K. Keeshan, O. Shestova, L. Xu, A. Bhandoola, and W. S. Pear The requirement for Notch signaling at the {beta}-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor J. Exp. Med., October 2, 2006; 203(10): 2239 - 2245. [Abstract] [Full Text] [PDF] C. J. Guidos Synergy between the pre-T cell receptor and Notch: cementing the {alpha}{beta} lineage choice J. Exp. Med., October 2, 2006; 203(10): 2233 - 2237. [Abstract] [Full Text] [PDF] S. Breit, M. Stanulla, T. Flohr, M. Schrappe, W.-D. Ludwig, G. Tolle, M. Happich, M. U. Muckenthaler, and A. E. Kulozik Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia Blood, August 15, 2006; 108(4): 1151 - 1157. [Abstract] [Full Text] [PDF] E. J. Reschly, C. Spaulding, T. Vilimas, W. V. Graham, R. L. Brumbaugh, I. Aifantis, W. S. Pear, and B. L. Kee Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms Blood, May 15, 2006; 107(10): 4115 - 4121. [Abstract] [Full Text] [PDF] I. Maillard, B. A. Schwarz, A. Sambandam, T. Fang, O. Shestova, L. Xu, A. Bhandoola, and W. S. Pear Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation Blood, May 1, 2006; 107(9): 3511 - 3519. [Abstract] [Full Text] [PDF] H. Shen, A. S. McElhinny, Y. Cao, P. Gao, J. Liu, R. Bronson, J. D. Griffin, and L. Wu The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis Genes & Dev., March 15, 2006; 20(6): 675 - 688. [Abstract] [Full Text] [PDF] P. A. Zweidler-McKay, Y. He, L. Xu, C. G. Rodriguez, F. G. Karnell, A. C. Carpenter, J. C. Aster, D. Allman, and W. S. Pear Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies Blood, December 1, 2005; 106(12): 3898 - 3906. [Abstract] [Full Text] [PDF] B. Srivastava, W. J. Quinn III, K. Hazard, J. Erikson, and D. Allman Characterization of marginal zone B cell precursors J. Exp. Med., November 7, 2005; 202(9): 1225 - 1234. [Abstract] [Full Text] [PDF] L. Tu, T. C. Fang, D. Artis, O. Shestova, S. E. Pross, I. Maillard, and W. S. Pear Notch signaling is an important regulator of type 2 immunity J. Exp. Med., October 17, 2005; 202(8): 1037 - 1042. [Abstract] [Full Text] [PDF] S. Landais, R. Quantin, and E. Rassart Radiation Leukemia Virus Common Integration at the Kis2 Locus: Simultaneous Overexpression of a Novel Noncoding RNA and of the Proximal Phf6 Gene J. Virol., September 1, 2005; 79(17): 11443 - 11456. [Abstract] [Full Text] [PDF]

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