|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 281, Issue 8, 5106-5119, February 24, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Target Selectivity of Vertebrate Notch Proteins
COLLABORATION BETWEEN DISCRETE DOMAINS AND CSL-BINDING SITE ARCHITECTURE DETERMINES ACTIVATION PROBABILITY*
11
¶12
From the
Departments of Molecular Biology and Pharmacology and of Medicine, Division of Dermatology, the Department of Genetics, and the ¶Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri 63110 and ||Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
All four mammalian Notch proteins interact with a single DNA-binding protein (RBP-j
), yet they are not equivalent in activating target genes. Parallel assays of three Notch-responsive promoters in several cell lines revealed that relative activation strength is dependent on protein module and promoter context more than the cellular context. Each Notch protein reads binding site orientation and distribution on the promoter differently; Notch1 performs extremely well on paired sites, and Notch3 prefers single sites in conjunction with a proximal zinc finger transcription factor. Although head-head sites can elicit a Notch response on their own, use of CBS (CSL binding site) in tail-tail orientation is context-dependent. Bias for specific DNA elements is achieved by interplay between the N-terminal RAM (RBP-j-associated molecule/ankyrin region), which interprets CBS proximity and orientation, and the C-terminal transactivation domain that interacts specifically with the transcription machinery or nearby factors. To confirm the prediction that modular design underscores the evolution of functional divergence between Notch proteins, we generated a synthetic Notch protein (Notch1 ankyrin with Notch3 transactivation domain) that displayed superior signaling strength on the hes5 promoter. Consistent with the prediction that "preferred" targets (Hes1) should respond faster and at lower Notch concentration than other targets, we showed that Hes5-GFP was extinguished fast and recovered slowly, whereas Hes1-GFP was inhibited late and recovered quickly after a pulse of DAPT in metanephroi cultures.
Received for publication, June 3, 2005 , and in revised form, December 9, 2005.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains Figs. S1-S4 and Table S1.
1 Supported by National Institutes of Health Grants GM55479-09 and HD44056, and by Washington University.
2 To whom correspondence should be addressed. E-mail: kopan{at}wustl.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Joshi, L. M. Minter, J. Telfer, R. M. Demarest, A. J. Capobianco, J. C. Aster, P. Sicinski, A. Fauq, T. E. Golde, and B. A. Osborne Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases Blood, February 19, 2009; 113(8): 1689 - 1698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. Gordon, K. L. Arnett, and S. C. Blacklow The molecular logic of Notch signaling - a structural and biochemical perspective J. Cell Sci., October 1, 2008; 121(19): 3109 - 3119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jin, E. M. Hansson, S. Tikka, F. Lanner, C. Sahlgren, F. Farnebo, M. Baumann, H. Kalimo, and U. Lendahl Notch Signaling Regulates Platelet-Derived Growth Factor Receptor-{beta} Expression in Vascular Smooth Muscle Cells Circ. Res., June 20, 2008; 102(12): 1483 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Waters, M. Y.J. Wu, T. Onay, J. Scutaru, J. Liu, C. G. Lobe, S. E. Quaggin, and T. D. Piscione Ectopic Notch Activation in Developing Podocytes Causes Glomerulosclerosis J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1139 - 1157. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sahlgren, M. V. Gustafsson, S. Jin, L. Poellinger, and U. Lendahl Notch signaling mediates hypoxia-induced tumor cell migration and invasion PNAS, April 29, 2008; 105(17): 6392 - 6397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Kathrein, S. Chari, and S. Winandy Ikaros Directly Represses the Notch Target Gene Hes1 in a Leukemia T Cell Line: IMPLICATIONS FOR CD4 REGULATION J. Biol. Chem., April 18, 2008; 283(16): 10476 - 10484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Li, Y. Li, W. Wu, W. R. Gordon, D. W. Chang, M. Lu, S. Scoggin, T. Fu, L. Vien, G. Histen, et al. Modulation of Notch Signaling by Antibodies Specific for the Extracellular Negative Regulatory Region of NOTCH3 J. Biol. Chem., March 21, 2008; 283(12): 8046 - 8054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yamaguchi, T. Oyama, E. Ito, H. Satoh, S. Azuma, M. Hayashi, K. Shimizu, R. Honma, Y. Yanagisawa, A. Nishikawa, et al. NOTCH3 Signaling Pathway Plays Crucial Roles in the Proliferation of ErbB2-Negative Human Breast Cancer Cells Cancer Res., March 15, 2008; 68(6): 1881 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kennard, H. Liu, and B. Lilly Transforming Growth Factor- (TGF- 1) Down-regulates Notch3 in Fibroblasts to Promote Smooth Muscle Gene Expression J. Biol. Chem., January 18, 2008; 283(3): 1324 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Clement, M. Gueguen, M. Glorian, R. Blaise, M. Andreani, C. Brou, P. Bausero, and I. Limon Notch3 and IL-1beta exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-{kappa}B drives crosstalk J. Cell Sci., October 1, 2007; 120(19): 3352 - 3361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Niessen and A. Karsan Notch signaling in the developing cardiovascular system Am J Physiol Cell Physiol, July 1, 2007; 293(1): C1 - C11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kopan, H.-T. Cheng, and K. Surendran Molecular Insights into Segmentation along the Proximal Distal Axis of the Nephron J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2014 - 2020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Hofmann and M. L. Iruela-Arispe Notch Signaling in Blood Vessels: Who Is Talking to Whom About What? Circ. Res., June 8, 2007; 100(11): 1556 - 1568. [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]
|
|
|
|
 |
|
 H.-T. Cheng, M. Kim, M. T. Valerius, K. Surendran, K. Schuster-Gossler, A. Gossler, A. P. McMahon, and R. Kopan Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron Development, February 15, 2007; 134(4): 801 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nam, P. Sliz, W. S. Pear, J. C. Aster, and S. C. Blacklow Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription PNAS, February 13, 2007; 104(7): 2103 - 2108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vooijs, C.-T. Ong, B. Hadland, S. Huppert, Z. Liu, J. Korving, M. van den Born, T. Stappenbeck, Y. Wu, H. Clevers, et al. Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE Development, February 1, 2007; 134(3): 535 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Weng, J. M. Millholland, Y. Yashiro-Ohtani, M. L. Arcangeli, A. Lau, C. Wai, C. del Bianco, C. G. Rodriguez, H. Sai, J. Tobias, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma Genes & Dev., August 1, 2006; 20(15): 2096 - 2109. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |