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Development, Vol 126, Issue 8 1689-1702, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
D Nofziger, A Miyamoto, KM Lyons and G Weinmaster
Department of Biological Chemistry, UCLA School of Medicine, Box 951737, Los Angeles, CA 90095-1737, USA. gweinmaster@mednet.ucla.edu
Notch signal transduction regulates expression of downstream genes through the activation of the DNA-binding protein Su(H)/CBF1. In Drosophila most of Notch signaling requires Su(H); however, some Notch-dependent processes occur in the absence of Su(H) suggesting that Notch signaling does not always involve activation of this factor. Using constitutively active forms of Notch lacking CBF1-interacting sequences we identified a Notch signaling pathway that inhibits myogenic differentiation of C2C12 myoblasts in the absence of CBF1 activation. Here we show that ligand-induced Notch signaling suppresses myogenesis in C2C12 myoblasts that express a dominant negative form of CBF1, providing additional evidence for CBF1-independent Notch signal transduction. Surprisingly mutant forms of Notch deficient in CBF1 activation are unable to antagonize MyoD activity, despite the fact that they inhibit myogenesis. Moreover, Notch-induced antagonism of MyoD requires CBF1 suggesting that the CBF1-dependent pathway mediates a cell-type-specific block in the myogenic program. However, Notch signaling in the absence of CBF1 activation blocks both myogenesis and osteogenesis, indicative of a general block in cellular differentiation. Taken together our data provide evidence for two distinct Notch signaling pathways that function to block differentiation at separate steps during the process of myogenesis in C2C12 myoblasts.
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S. Jeffries and A. J. Capobianco Neoplastic Transformation by Notch Requires Nuclear Localization Mol. Cell. Biol., June 1, 2000; 20(11): 3928 - 3941. [Abstract] [Full Text]
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S. Zhou, M. Fujimuro, J. J.-D. Hsieh, L. Chen, A. Miyamoto, G. Weinmaster, and S. D. Hayward SKIP, a CBF1-Associated Protein, Interacts with the Ankyrin Repeat Domain of NotchIC To Facilitate NotchIC Function Mol. Cell. Biol., April 1, 2000; 20(7): 2400 - 2410. [Abstract] [Full Text]
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A. Tavares, T Tsukui, and J. Izpisua Belmonte Evidence that members of the Cut/Cux/CDP family may be involved in AER positioning and polarizing activity during chick limb development Development, January 12, 2000; 127(23): 5133 - 5144. [Abstract] [PDF]
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M Delfini, E Hirsinger, O Pourquie, and D Duprez Delta 1-activated notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis Development, January 12, 2000; 127(23): 5213 - 5224. [Abstract] [PDF]
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M. Rones, K. McLaughlin, M Raffin, and M Mercola Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis Development, January 9, 2000; 127(17): 3865 - 3876. [Abstract] [PDF]
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T Klein, L Seugnet, M Haenlin, and A Martinez Arias Two different activities of Suppressor of Hairless during wing development in Drosophila Development, January 8, 2000; 127(16): 3553 - 3566. [Abstract] [PDF]
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N. Sestan, S. Artavanis-Tsakonas, and P. Rakic Contact-Dependent Inhibition of Cortical Neurite Growth Mediated by Notch Signaling Science, October 22, 1999; 286(5440): 741 - 746. [Abstract] [Full Text]
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 W. PEAR, Z. TANG, S. DEROCCO, D. ALLMAN, R. HARDY, J. PUI, L. XU, F. KARNELL, J. ASTER, and T. KADESCH Consequences of Notch-mediated Inhibition of the Transcription Factor E47 Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 33 - 38. [Abstract] [PDF]
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L. T. Lam, C. Ronchini, J. Norton, A. J. Capobianco, and E. H. Bresnick Suppression of Erythroid but Not Megakaryocytic Differentiation of Human K562 Erythroleukemic Cells by Notch-1 J. Biol. Chem., June 23, 2000; 275(26): 19676 - 19684. [Abstract] [Full Text] [PDF]
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T. Morimura, R. Goitsuka, Y. Zhang, I. Saito, M. Reth, and D. Kitamura Cell Cycle Arrest and Apoptosis Induced by Notch1 in B Cells J. Biol. Chem., November 17, 2000; 275(47): 36523 - 36531. [Abstract] [Full Text] [PDF]
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D. Small, D. Kovalenko, D. Kacer, L. Liaw, M. Landriscina, C. Di Serio, I. Prudovsky, and T. Maciag Soluble Jagged 1 Represses the Function of Its Transmembrane Form to Induce the Formation of the Src-dependent Chord-like Phenotype J. Biol. Chem., August 17, 2001; 276(34): 32022 - 32030. [Abstract] [Full Text] [PDF]
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N. Yamamoto, S.-i. Yamamoto, F. Inagaki, M. Kawaichi, A. Fukamizu, N. Kishi, K. Matsuno, K. Nakamura, G. Weinmaster, H. Okano, et al. Role of Deltex-1 as a Transcriptional Regulator Downstream of the Notch Receptor J. Biol. Chem., November 21, 2001; 276(48): 45031 - 45040. [Abstract] [Full Text] [PDF]
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X. Gao, T. Chandra, M.-O. Gratton, I. Quelo, J. Prud'homme, S. Stifani, and R. St-Arnaud HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program J. Cell Biol., September 17, 2001; 154(6): 1161 - 1172. [Abstract] [Full Text] [PDF]
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