Previous Article | Next Article 
Molecular and Cellular Biology, January 2002, p. 12-22, Vol. 22, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.22.1.12-22.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
c-Jun and Hypoxia-Inducible Factor 1 Functionally Cooperate in Hypoxia-Induced Gene Transcription
Arántzazu Alfranca, M. Dolores Gutiérrez, Alicia Vara, Julián Aragonés, Felipe Vidal, and Manuel O. Landázuri*
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
Received 2 August 2001/
Accepted 20 September 2001
Under low-oxygen conditions, cells develop an adaptive program that leads to the induction of several genes, which are transcriptionally regulated by hypoxia-inducible factor 1 (HIF-1). On the other hand, there are other factors which modulate the HIF-1-mediated induction of some genes by binding to cis-acting motifs present in their promoters. Here, we show that c-Jun functionally cooperates with HIF-1 transcriptional activity in different cell types. Interestingly, a dominant-negative mutant of c-Jun which lacks its transactivation domain partially inhibits HIF-1-mediated transcription. This cooperative effect is not due to an increase in the nuclear amount of the HIF-1
subunit, nor does it require direct binding of c-Jun to DNA. c-Jun and HIF-1
are able to associate in vivo but not in vitro, suggesting that this interaction involves the participation of additional proteins and/or a posttranslational modification of these factors. In this context, hypoxia induces phosphorylation of c-Jun at Ser63 in endothelial cells. This process is involved in its cooperative effect, since specific blockade of the JNK pathway and mutation of c-Jun at Ser63 and Ser73 impair its functional cooperation with HIF-1. The functional interplay between c-Jun and HIF-1 provides a novel insight into the regulation of some genes, such as the one for VEGF, which is a key regulator of tumor angiogenesis.
* Corresponding author. Mailing address: Servicio de Inmunología, Hospital de la Princesa, Diego de León 62, 28006 Madrid, Spain. Phone: 34-91-5202662. Fax: 34-91-5202374. E-mail: mortiz{at}hlpr.insalud.es.
Molecular and Cellular Biology, January 2002, p. 12-22, Vol. 22, No. 1
0022-538X/01/$04.00+0 DOI: 10.1128/MCB.22.1.12-22.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Alfranca, A., Lopez-Oliva, J. M., Genis, L., Lopez-Maderuelo, D., Mirones, I., Salvado, D., Quesada, A. J., Arroyo, A. G., Redondo, J. M.
(2008). PGE2 induces angiogenesis via MT1-MMP-mediated activation of the TGF{beta}/Alk5 signaling pathway. Blood
112: 1120-1128
[Abstract]
[Full Text]
-
Blanco, S., Santos, C., Lazo, P. A.
(2007). Vaccinia-Related Kinase 2 Modulates the Stress Response to Hypoxia Mediated by TAK1. Mol. Cell. Biol.
27: 7273-7283
[Abstract]
[Full Text]
-
Mense, S. M., Sengupta, A., Zhou, M., Lan, C., Bentsman, G., Volsky, D. J., Zhang, L.
(2006). Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in primary human astrocytes. Physiol. Genomics
25: 435-449
[Abstract]
[Full Text]
-
Wang, J., Weigand, L., Wang, W., Sylvester, J. T., Shimoda, L. A.
(2005). Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery. Am. J. Physiol. Lung Cell. Mol. Physiol.
288: L1049-L1058
[Abstract]
[Full Text]
-
Comerford, K. M., Cummins, E. P., Taylor, C. T.
(2004). c-Jun NH2-Terminal Kinase Activation Contributes to Hypoxia-Inducible Factor 1{alpha}-Dependent P-Glycoprotein Expression in Hypoxia. Cancer Res.
64: 9057-9061
[Abstract]
[Full Text]
-
Laderoute, K. R., Calaoagan, J. M., Knapp, M., Johnson, R. S.
(2004). Glucose Utilization Is Essential for Hypoxia-Inducible Factor 1{alpha}-Dependent Phosphorylation of c-Jun. Mol. Cell. Biol.
24: 4128-4137
[Abstract]
[Full Text]
-
Hopfl, G., Ogunshola, O., Gassmann, M.
(2004). HIFs and tumors--causes and consequences. Am. J. Physiol. Regul. Integr. Comp. Physiol.
286: R608-R623
[Abstract]
[Full Text]
-
Mizukami, Y., Li, J., Zhang, X., Zimmer, M. A., Iliopoulos, O., Chung, D. C.
(2004). Hypoxia-Inducible Factor-1-Independent Regulation of Vascular Endothelial Growth Factor by Hypoxia in Colon Cancer. Cancer Res.
64: 1765-1772
[Abstract]
[Full Text]
-
Qi, X., Borowicz, S., Pramanik, R., Schultz, R. M., Han, J., Chen, G.
(2004). Estrogen Receptor Inhibits c-Jun-dependent Stress-induced Cell Death by Binding and Modifying c-Jun Activity in Human Breast Cancer Cells. J. Biol. Chem.
279: 6769-6777
[Abstract]
[Full Text]
-
Short, M., Nemenoff, R. A., Zawada, W. M., Stenmark, K. R., Das, M.
(2004). Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts. Am. J. Physiol. Cell Physiol.
286: C416-C425
[Abstract]
[Full Text]
-
del Peso, L., Castellanos, M. C., Temes, E., Martin-Puig, S., Cuevas, Y., Olmos, G., Landazuri, M. O.
(2003). The von Hippel Lindau/Hypoxia-inducible Factor (HIF) Pathway Regulates the Transcription of the HIF-Proline Hydroxylase Genes in Response to Low Oxygen. J. Biol. Chem.
278: 48690-48695
[Abstract]
[Full Text]
-
Kunz, M., Moeller, S., Koczan, D., Lorenz, P., Wenger, R. H., Glocker, M. O., Thiesen, H.-J., Gross, G., Ibrahim, S. M.
(2003). Mechanisms of Hypoxic Gene Regulation of Angiogenesis Factor Cyr61 in Melanoma Cells. J. Biol. Chem.
278: 45651-45660
[Abstract]
[Full Text]
-
Godard, S., Getz, G., Delorenzi, M., Farmer, P., Kobayashi, H., Desbaillets, I., Nozaki, M., Diserens, A.-C., Hamou, M.-F., Dietrich, P.-Y., Regli, L., Janzer, R. C., Bucher, P., Stupp, R., de Tribolet, N., Domany, E., Hegi, M. E.
(2003). Classification of Human Astrocytic Gliomas on the Basis of Gene Expression: A Correlated Group of Genes with Angiogenic Activity Emerges As a Strong Predictor of Subtypes. Cancer Res.
63: 6613-6625
[Abstract]
[Full Text]
-
Kodama, T., Shimizu, N., Yoshikawa, N., Makino, Y., Ouchida, R., Okamoto, K., Hisada, T., Nakamura, H., Morimoto, C., Tanaka, H.
(2003). Role of the Glucocorticoid Receptor for Regulation of Hypoxia-dependent Gene Expression. J. Biol. Chem.
278: 33384-33391
[Abstract]
[Full Text]
-
Duyndam, M. C. A., Hulscher, S. T. M., van der Wall, E., Pinedo, H. M., Boven, E.
(2003). Evidence for a Role of p38 Kinase in Hypoxia-inducible Factor 1-independent Induction of Vascular Endothelial Growth Factor Expression by Sodium Arsenite. J. Biol. Chem.
278: 6885-6895
[Abstract]
[Full Text]
-
Burroughs, K. D., Oh, J., Barrett, J. C., DiAugustine, R. P.
(2003). Phosphatidylinositol 3-Kinase and Mek1/2 Are Necessary for Insulin-Like Growth Factor-I-Induced Vascular Endothelial Growth Factor Synthesis in Prostate Epithelial Cells: A Role for Hypoxia-Inducible Factor-1?. Mol Cancer Res
1: 312-322
[Abstract]
[Full Text]
Copyright © 2002 by the American Society for Microbiology. All rights reserved.