|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 126, Issue 22 5097-5106, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
QT Wang and RA Holmgren
Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA.
Cubitus interruptus (Ci), a Drosophila transcription factor, mediates Hedgehog (Hh) signaling during the patterning of embryonic epidermis and larval imaginal discs. In the absence of Hh signal, Ci is cleaved to generate a truncated nuclear form capable of transcriptional repression. Hh signaling stabilizes and activates the full-length Ci protein leading to strong activation of downstream target genes including patched and decapentaplegic. A number of molecules have been implicated in the regulation of Ci. Mutations in these molecules lead to changes in Ci protein level, the extent of Ci proteolysis and the expression of Ci target genes. This paper examines the regulation of Ci subcellular localization and activity. We first characterize a bipartite nuclear localization signal (NLS) within Ci. We propose that the subcellular distribution of Ci is affected by two opposing forces, the action of the NLS and that of at least two regions targeting Ci to the cytoplasm. Further our data show that loss of PKA or Costal-2 activity does not fully mimic Hh signaling, demonstrating that Ci proteolysis and Ci activation are two distinct events which are regulated through different paths. Finally, we propose that there are three levels of apparent Ci activity, corresponding to three zones along the AP axis with different sets of gene expression and different levels of Hh signaling.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  S. F. Farzan, M. A. Stegman, S. K. Ogden, M. Ascano Jr, K. E. Black, O. Tacchelly, and D. J. Robbins A Quantification of Pathway Components Supports a Novel Model of Hedgehog Signal Transduction J. Biol. Chem., October 16, 2009; 284(42): 28874 - 28884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. O.-L. Cheung, X. Zhang, A. Ribeiro, R. Mo, S. Makino, V. Puviindran, K. K. L. Law, J. Briscoe, and C.-c. Hui The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling Sci. Signal., June 23, 2009; 2(76): ra29 - ra29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Mingot, S. Vega, B. Maestro, J. M. Sanz, and M. A. Nieto Characterization of Snail nuclear import pathways as representatives of C2H2 zinc finger transcription factors J. Cell Sci., May 1, 2009; 122(9): 1452 - 1460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hatayama, T. Tomizawa, K. Sakai-Kato, P. Bouvagnet, S. Kose, N. Imamoto, S. Yokoyama, N. Utsunomiya-Tate, K. Mikoshiba, T. Kigawa, et al. Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain Hum. Mol. Genet., November 15, 2008; 17(22): 3459 - 3473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-C. Tien, A. Rajan, K. L. Schulze, H. D. Ryoo, M. Acar, H. Steller, and H. J. Bellen Ero1L, a thiol oxidase, is required for Notch signaling through cysteine bridge formation of the Lin12-Notch repeats in Drosophila melanogaster J. Cell Biol., September 22, 2008; 182(6): 1113 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Friggi-Grelin, L. Lavenant-Staccini, and P. Therond Control of Antagonistic Components of the Hedgehog Signaling Pathway by microRNAs in Drosophila Genetics, May 1, 2008; 179(1): 429 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, X. Cao, J. Jiang, and J. Jia Fused Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation Genes & Dev., August 1, 2007; 21(15): 1949 - 1963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Pan and B. Wang A Novel Protein-processing Domain in Gli2 and Gli3 Differentially Blocks Complete Protein Degradation by the Proteasome J. Biol. Chem., April 13, 2007; 282(15): 10846 - 10852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Walthall, M. Moses, and J. I. Horabin A large complex containing Patched and Smoothened initiates Hedgehog signaling in Drosophila J. Cell Sci., March 1, 2007; 120(5): 826 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhou, S. Kim, S. Ishii, and T. G. Boyer Mediator Modulates Gli3-Dependent Sonic Hedgehog Signaling Mol. Cell. Biol., December 1, 2006; 26(23): 8667 - 8682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Dasari, M. Gallup, H. Lemjabbar, I. Maltseva, and N. McNamara Epithelial-Mesenchymal Transition in Lung Cancer: Is Tobacco the "Smoking Gun"? Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 3 - 9. [Full Text] [PDF]
|
|
|
|
|
|
Y. Pan, C. B. Bai, A. L. Joyner, and B. Wang Sonic hedgehog Signaling Regulates Gli2 Transcriptional Activity by Suppressing Its Processing and Degradation. Mol. Cell. Biol., May 1, 2006; 26(9): 3365 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Ogden, D. J. Casso, M. Ascano Jr., M. M. Yore, T. B. Kornberg, and D. J. Robbins Smoothened Regulates Activator and Repressor Functions of Hedgehog Signaling via Two Distinct Mechanisms J. Biol. Chem., March 17, 2006; 281(11): 7237 - 7243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sheng, S. Chi, X. Zhang, and J. Xie Regulation of Gli1 Localization by the cAMP/Protein Kinase A Signaling Axis through a Site Near the Nuclear Localization Signal J. Biol. Chem., January 6, 2006; 281(1): 9 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wang and Y. Li Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing PNAS, January 3, 2006; 103(1): 33 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Ho, K. Suyama, M. Fish, and M. P. Scott Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused Development, March 15, 2005; 132(6): 1401 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Tay, P. W. Ingham, and S. Roy A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo Development, February 15, 2005; 132(4): 625 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhang, E. H. Williams, Y. Guo, L. Lum, and P. A. Beachy Inaugural Article: Extensive phosphorylation of Smoothened in Hedgehog pathway activation PNAS, December 28, 2004; 101(52): 17900 - 17907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lum and P. A. Beachy The Hedgehog Response Network: Sensors, Switches, and Routers Science, June 18, 2004; 304(5678): 1755 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sekimizu, N. Nishioka, H. Sasaki, H. Takeda, R. O. Karlstrom, and A. Kawakami The zebrafish iguana locus encodes Dzip1, a novel zinc-finger protein required for proper regulation of Hedgehog signaling Development, June 1, 2004; 131(11): 2521 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kwon, R. Hays, J. Fetting, and T. V. Orenic Opposing inputs by Hedgehog and Brinker define a stripe of hairy expression in the Drosophila leg imaginal disc Development, June 1, 2004; 131(11): 2681 - 2692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Stegman, J. A. Goetz, M. Ascano Jr., S. K. Ogden, K. E. Nybakken, and D. J. Robbins The Kinesin-related Protein Costal2 Associates with Membranes in a Hedgehog-sensitive, Smoothened-independent Manner J. Biol. Chem., February 20, 2004; 279(8): 7064 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jia, C. Tong, and J. Jiang Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail Genes & Dev., November 1, 2003; 17(21): 2709 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Hooper Smoothened translates Hedgehog levels into distinct responses Development, September 1, 2003; 130(17): 3951 - 3963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Karlstrom, O. V. Tyurina, A. Kawakami, N. Nishioka, W. S. Talbot, H. Sasaki, and A. F. Schier Genetic analysis of zebrafish gli1 and gli2 reveals divergent requirements for gli genes in vertebrate development Development, April 15, 2003; 130(8): 1549 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jiang Degrading Ci: who is Cul-pable? Genes & Dev., September 15, 2002; 16(18): 2315 - 2321. [Full Text] [PDF]
|
|
|
|
|
|
M. Ascano Jr., K. E. Nybakken, J. Sosinski, M. A. Stegman, and D. J. Robbins The Carboxyl-Terminal Domain of the Protein Kinase Fused Can Function as a Dominant Inhibitor of Hedgehog Signaling Mol. Cell. Biol., March 1, 2002; 22(5): 1555 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Kroft, J. Patterson, J. Won Yoon, L. Doglio, D. O. Walterhouse, P. M. Iannaccone, and E. Goldberg GLI1 Localization in the Germinal Epithelial Cells Alternates Between Cytoplasm and Nucleus: Upregulation in Transgenic Mice Blocks Spermatogenesis in Pachytene Biol Reprod, December 1, 2001; 65(6): 1663 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fukumoto, R. Watanabe-Fukunaga, K. Fujisawa, S. Nagata, and R. Fukunaga The Fused Protein Kinase Regulates Hedgehog-stimulated Transcriptional Activation in Drosophila Schneider 2 Cells J. Biol. Chem., October 12, 2001; 276(42): 38441 - 38448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kiger Jr. and C. O'Shea Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila Genetics, July 1, 2001; 158(3): 1157 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Mingot, E. A. Espeso, E. Díez, and M. A. Peñalva Ambient pH Signaling Regulates Nuclear Localization of the Aspergillus nidulans PacC Transcription Factor Mol. Cell. Biol., March 1, 2001; 21(5): 1688 - 1699. [Abstract] [Full Text]
|
|
|
|
|
|
G. Wang, K. Amanai, B. Wang, and J. Jiang Interactions with Costal2 and Suppressor of fused regulate nuclear translocation and activity of Cubitus interruptus Genes & Dev., November 15, 2000; 14(22): 2893 - 2905. [Abstract] [Full Text]
|
|
|
|
|
|
A Gallet, C Angelats, S Kerridge, and P. Therond Cubitus interruptus-independent transduction of the Hedgehog signal in Drosophila Development, January 12, 2000; 127(24): 5509 - 5522. [Abstract] [PDF]
|
|
|
|
|
|
N Methot and K Basler Suppressor of fused opposes hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus Development, January 9, 2000; 127(18): 4001 - 4010. [Abstract] [PDF]
|
|
|
|
|
|
Q. Wang and R. Holmgren Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci activation Development, January 7, 2000; 127(14): 3131 - 3139. [Abstract] [PDF]
|
|
|
|
|
|
V. M. Chennathukuzhi, Y. Kurihara, J. D. Bray, and N. B. Hecht Trax (Translin-associated Factor X), a Primarily Cytoplasmic Protein, Inhibits the Binding of TB-RBP (Translin) to RNA J. Biol. Chem., April 13, 2001; 276(16): 13256 - 13263. [Abstract] [Full Text] [PDF]
|
|
