This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lavista-Llanos, S.
Right arrow Articles by Wappner, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lavista-Llanos, S.
Right arrow Articles by Wappner, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2002, p. 6842-6853, Vol. 22, No. 19
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.19.6842-6853.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Control of the Hypoxic Response in Drosophila melanogaster by the Basic Helix-Loop-Helix PAS Protein Similar

Sofía Lavista-Llanos,1 Lázaro Centanin,1 Maximiliano Irisarri,1 Daniela M. Russo,1 Jonathan M. Gleadle,2 Silvia N. Bocca,1 Mariana Muzzopappa,1 Peter J. Ratcliffe,2 and Pablo Wappner1*

Instituto de Investigaciones Bioquímicas Fundación Campomar, Buenos Aires 1405, Argentina,1 The Henry Wellcome Building of Genomic Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom2

Received 19 February 2002/ Returned for modification 10 May 2002/ Accepted 12 June 2002

In mammalian systems, the heterodimeric basic helix-loop-helix (bHLH)-PAS transcription hypoxia-inducible factor (HIF) has emerged as the key regulator of responses to hypoxia. Here we define a homologous system in Drosophila melanogaster, and we characterize its activity in vivo during development. By using transcriptional reporters in developing transgenic flies, we show that hypoxia-inducible activity rises to a peak in late embryogenesis and is most pronounced in tracheal cells. We show that the bHLH-PAS proteins Similar (Sima) and Tango (Tgo) function as HIF-{alpha} and HIF-ß homologues, respectively, and demonstrate a conserved mode of regulation for Sima by oxygen. Sima protein, but not its mRNA, was upregulated in hypoxia. Time course experiments following pulsed ectopic expression demonstrated that Sima is stabilized in hypoxia and that degradation relies on a central domain encompassing amino acids 692 to 863. Continuous ectopic expression overrode Sima degradation, which remained cytoplasmic in normoxia, and translocated to the nucleus only in hypoxia, revealing a second oxygen-regulated activation step. Abrogation of the Drosophila Egl-9 prolyl hydroxylase homologue, CG1114, caused both stabilization and nuclear localization of Sima, indicating a central involvement in both processes. Tight conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new focus for understanding oxygen homeostasis in intact multicellular organisms.

* Corresponding author. Mailing address: Instituto de Investigaciones Bioquímicas Fundación Campomar, Patricias Argentinas 435, Buenos Aires 1405, Argentina. Phone: (54-11) 4863-4011. Fax: (54-11) 4865-2246. E-mail: pwappner{at}leloir.org.ar.

Molecular and Cellular Biology, October 2002, p. 6842-6853, Vol. 22, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.19.6842-6853.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Helenius, I. T., Krupinski, T., Turnbull, D. W., Gruenbaum, Y., Silverman, N., Johnson, E. A., Sporn, P. H. S., Sznajder, J. I., Beitel, G. J. (2009). Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection. Proc. Natl. Acad. Sci. USA 106: 18710-18715 [Abstract] [Full Text]  
  • Dijkers, P. F., O'Farrell, P. H. (2009). Dissection of a Hypoxia-induced, Nitric Oxide-mediated Signaling Cascade. Mol. Biol. Cell 20: 4083-4090 [Abstract] [Full Text]  
  • Irisarri, M., Lavista-Llanos, S., Romero, N. M., Centanin, L., Dekanty, A., Wappner, P. (2009). Central Role of the Oxygen-dependent Degradation Domain of Drosophila HIF{alpha}/Sima in Oxygen-dependent Nuclear Export. Mol. Biol. Cell 20: 3878-3887 [Abstract] [Full Text]  
  • Romero, N. M., Irisarri, M., Roth, P., Cauerhff, A., Samakovlis, C., Wappner, P. (2008). Regulation of the Drosophila Hypoxia-Inducible Factor {alpha} Sima by CRM1-Dependent Nuclear Export. Mol. Cell. Biol. 28: 3410-3423 [Abstract] [Full Text]  
  • Jiang, L., Crews, S. T. (2007). Transcriptional Specificity of Drosophila Dysfusion and the Control of Tracheal Fusion Cell Gene Expression. J. Biol. Chem. 282: 28659-28668 [Abstract] [Full Text]  
  • Pandey, R., Heeger, S., Lehner, C. F. (2007). Rapid effects of acute anoxia on spindle kinetochore interactions activate the mitotic spindle checkpoint. J. Cell Sci. 120: 2807-2818 [Abstract] [Full Text]  
  • Huang, H., Haddad, G. G. (2007). Drosophila dMRP4 regulates responsiveness to O2 deprivation and development under hypoxia. Physiol. Genomics 29: 260-266 [Abstract] [Full Text]  
  • Chen, M., Lopes, J. M. (2007). Multiple Basic Helix-Loop-Helix Proteins Regulate Expression of the ENO1 Gene of Saccharomyces cerevisiae. Eukaryot Cell 6: 786-796 [Abstract] [Full Text]  
  • Baird, N. A., Turnbull, D. W., Johnson, E. A. (2006). Induction of the Heat Shock Pathway during Hypoxia Requires Regulation of Heat Shock Factor by Hypoxia-inducible Factor-1. J. Biol. Chem. 281: 38675-38681 [Abstract] [Full Text]  
  • Jiang, L., Crews, S. T. (2006). dysfusion Transcriptional Control of Drosophila Tracheal Migration, Adhesion, and Fusion.. Mol. Cell. Biol. 26: 6547-6556 [Abstract] [Full Text]  
  • Hopfer, U., Hopfer, H., Jablonski, K., Stahl, R. A. K., Wolf, G. (2006). The Novel WD-repeat Protein Morg1 Acts as a Molecular Scaffold for Hypoxia-inducible Factor Prolyl Hydroxylase 3 (PHD3). J. Biol. Chem. 281: 8645-8655 [Abstract] [Full Text]  
  • Umetsu, D., Murakami, S., Sato, M., Tabata, T. (2006). The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in the Drosophila visual system. Development 133: 791-800 [Abstract] [Full Text]  
  • Dekanty, A., Lavista-Llanos, S., Irisarri, M., Oldham, S., Wappner, P. (2005). The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-{alpha}/Sima. J. Cell Sci. 118: 5431-5441 [Abstract] [Full Text]  
  • Treins, C., Giorgetti-Peraldi, S., Murdaca, J., Monthouel-Kartmann, M.-N., Van Obberghen, E. (2005). Regulation of Hypoxia-Inducible Factor (HIF)-1 Activity and Expression of HIF Hydroxylases in Response to Insulin-Like Growth Factor I. Mol. Endocrinol. 19: 1304-1317 [Abstract] [Full Text]  
  • Cabernard, C., Neumann, M., Affolter, M. (2004). Cellular and molecular mechanisms involved in branching morphogenesis of the Drosophila tracheal system. J. Appl. Physiol. 97: 2347-2353 [Abstract] [Full Text]  
  • Reiling, J. H., Hafen, E. (2004). The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 18: 2879-2892 [Abstract] [Full Text]  
  • Emmerich, J., Meyer, C. A., de la Cruz, A. F. A., Edgar, B. A., Lehner, C. F. (2004). Cyclin D Does Not Provide Essential Cdk4-Independent Functions in Drosophila. Genetics 168: 867-875 [Abstract] [Full Text]  
  • Henry, J. R., Harrison, J. F. (2004). Plastic and evolved responses of larval tracheae and mass to varying atmospheric oxygen content in Drosophila melanogaster. J. Exp. Biol. 207: 3559-3567 [Abstract] [Full Text]  
  • Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., Gleadle, J. M. (2004). Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor. J. Biol. Chem. 279: 38458-38465 [Abstract] [Full Text]  
  • Gorr, T. A., Cahn, J. D., Yamagata, H., Bunn, H. F. (2004). Hypoxia-induced Synthesis of Hemoglobin in the Crustacean Daphnia magna Is Hypoxia-inducible Factor-dependent. J. Biol. Chem. 279: 36038-36047 [Abstract] [Full Text]  
  • Gorr, T. A., Tomita, T., Wappner, P., Bunn, H. F. (2004). Regulation of Drosophila Hypoxia-inducible Factor (HIF) Activity in SL2 Cells: IDENTIFICATION OF A HYPOXIA-INDUCED VARIANT ISOFORM OF THE HIF{alpha} HOMOLOG GENE similar. J. Biol. Chem. 279: 36048-36058 [Abstract] [Full Text]  
  • Greenlee, K. J., Harrison, J. F. (2004). Development of respiratory function in the American locust Schistocerca americana I. Across-instar effects. J. Exp. Biol. 207: 497-508 [Abstract] [Full Text]  
  • Smulders-Srinivasan, T. K., Lin, H. (2003). Screens for piwi Suppressors in Drosophila Identify Dosage-Dependent Regulators of Germline Stem Cell Division. Genetics 165: 1971-1991 [Abstract] [Full Text]  
  • Bruick, R. K. (2003). Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev. 17: 2614-2623 [Full Text]  
  • Maxwell, P. (2003). HIF-1: An Oxygen Response System with Special Relevance to the Kidney. J. Am. Soc. Nephrol. 14: 2712-2722 [Full Text]  
  • Gardocki, M. E., Lopes, J. M. (2003). Expression of the Yeast PIS1 Gene Requires Multiple Regulatory Elements Including a Rox1p Binding Site. J. Biol. Chem. 278: 38646-38652 [Abstract] [Full Text]  
  • Jiang, L., Crews, S. T. (2003). The Drosophila dysfusion Basic Helix-Loop-Helix (bHLH)-PAS Gene Controls Tracheal Fusion and Levels of the Trachealess bHLH-PAS Protein. Mol. Cell. Biol. 23: 5625-5637 [Abstract] [Full Text]  
  • Masson, N., Ratcliffe, P. J. (2003). HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O2 levels. J. Cell Sci. 116: 3041-3049 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»