QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 14, Issue 6, 2216-2225, June 2003

This Article Full Text Full Text (PDF) All Versions of this Article: E02-09-0598v1 14/6/2216    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, J. Articles by Brüne, B. Search for Related Content PubMed PubMed Citation Articles by Zhou, J. Articles by Brüne, B.

Tumor Necrosis Factor- Causes Accumulation of a Ubiquitinated Form of Hypoxia Inducible Factor-1 through a Nuclear Factor-B-Dependent Pathway

Jie Zhou ^*, Tobias Schmid ^*, and Bernhard Brüne  ^* 

^* Department of Cell Biology, Faculty of Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany

Submitted September 18, 2002; Accepted January 30, 2003
Monitoring Editor: Keith R. Yamamoto

Hypoxia-inducible factor-1 (HIF-1) is a regulator of metabolic adaptation to hypoxia. It is now appreciated that HIF-1 accumulation is achieved under normoxic conditions by various factors, such as TNF-. Here, it was our intention to gain insight into the signaling mechanisms used by TNF- to stimulate HIF-1. In tubular LLC-PK₁ or human embryonic kidney cells, TNF- induced accumulation of HIF-1 protein but not HIF-1 mRNA. Blocking nuclear factor (NF)-B with sulfasalazine or expression of an IB superrepressor attenuated HIF-1 accumulation, whereas transfection of active p50/p65-NF-B subunits mimicked a TNF- response. Experiments with actinomycin D and cycloheximide also pointed to a transcriptional and translational process in facilitating the TNF- response. Interestingly, and in contrast to established hypoxic signaling concepts, TNF- elicited HIF-1 accumulation in a ubiquitinated form that still bound the von Hippel-Lindau (pVHL) protein. These data indicate that HIF-1 accumulation by TNF- demands the NF-B pathway, preserves ubiquitination of HIF-1, and allows the HIF-1-pVHL interaction.

This article has been cited by other articles:

				S. A. Gerber and J. S. Pober IFN-{alpha} Induces Transcription of Hypoxia-Inducible Factor-1{alpha} to Inhibit Proliferation of Human Endothelial Cells J. Immunol., July 15, 2008; 181(2): 1052 - 1062. [Abstract] [Full Text] [PDF]

				J. C. Sluimer, J.-M. Gasc, J. L. van Wanroij, N. Kisters, M. Groeneweg, M. D. Sollewijn Gelpke, J. P. Cleutjens, L. H. van den Akker, P. Corvol, B. G. Wouters, et al. Hypoxia, Hypoxia-Inducible Transcription Factor, and Macrophages in Human Atherosclerotic Plaques Are Correlated With Intraplaque Angiogenesis J. Am. Coll. Cardiol., April 1, 2008; 51(13): 1258 - 1265. [Abstract] [Full Text] [PDF]

				A. Tzouvelekis, V. Harokopos, T. Paparountas, N. Oikonomou, A. Chatziioannou, G. Vilaras, E. Tsiambas, A. Karameris, D. Bouros, and V. Aidinis Comparative Expression Profiling in Pulmonary Fibrosis Suggests a Role of Hypoxia-inducible Factor-1{alpha} in Disease Pathogenesis Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1108 - 1119. [Abstract] [Full Text] [PDF]

				B. Brune and J. Zhou Nitric oxide and superoxide: Interference with hypoxic signaling Cardiovasc Res, July 15, 2007; 75(2): 275 - 282. [Abstract] [Full Text] [PDF]

				S. Bonello, C. Zahringer, R. S. BelAiba, T. Djordjevic, J. Hess, C. Michiels, T. Kietzmann, and A. Gorlach Reactive Oxygen Species Activate the HIF-1{alpha} Promoter Via a Functional NF{kappa}B Site Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 755 - 761. [Abstract] [Full Text] [PDF]

				D. Viemann, M. Schmidt, K. Tenbrock, S. Schmid, V. Muller, K. Klimmek, S. Ludwig, J. Roth, and M. Goebeler The Contact Allergen Nickel Triggers a Unique Inflammatory and Proangiogenic Gene Expression Pattern via Activation of NF-{kappa}B and Hypoxia-Inducible Factor-1{alpha} J. Immunol., March 1, 2007; 178(5): 3198 - 3207. [Abstract] [Full Text] [PDF]

				S. McMahon, M. Charbonneau, S. Grandmont, D. E. Richard, and C. M. Dubois Transforming Growth Factor beta1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression J. Biol. Chem., August 25, 2006; 281(34): 24171 - 24181. [Abstract] [Full Text] [PDF]

				H.-G. Zhang, C. Liu, K. Su, S. Yu, L. Zhang, S. Zhang, J. Wang, X. Cao, W. Grizzle, and R. P. Kimberly A Membrane Form of TNF-{alpha} Presented by Exosomes Delays T Cell Activation-Induced Cell Death. J. Immunol., June 15, 2006; 176(12): 7385 - 7393. [Abstract] [Full Text] [PDF]

				H. Lu, W. Ouyang, and C. Huang Inflammation, a Key Event in Cancer Development Mol. Cancer Res., April 1, 2006; 4(4): 221 - 233. [Abstract] [Full Text] [PDF]

				D. Tirziu, K. L. Moodie, Z. W. Zhuang, K. Singer, A. Helisch, J. F. Dunn, W. Li, J. Singh, and M. Simons Delayed Arteriogenesis in Hypercholesterolemic Mice Circulation, October 18, 2005; 112(16): 2501 - 2509. [Abstract] [Full Text] [PDF]

				S. McMahon, F. Grondin, P. P. McDonald, D. E. Richard, and C. M. Dubois Hypoxia-enhanced Expression of the Proprotein Convertase Furin Is Mediated by Hypoxia-inducible Factor-1: IMPACT ON THE BIOACTIVATION OF PROPROTEINS J. Biol. Chem., February 25, 2005; 280(8): 6561 - 6569. [Abstract] [Full Text] [PDF]

				S. Frantz, K. A. Vincent, O. Feron, and R. A. Kelly Innate Immunity and Angiogenesis Circ. Res., January 7, 2005; 96(1): 15 - 26. [Abstract] [Full Text] [PDF]

				S. R. Walmsley, C. Print, N. Farahi, C. Peyssonnaux, R. S. Johnson, T. Cramer, A. Sobolewski, A. M. Condliffe, A. S. Cowburn, N. Johnson, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1{alpha}-dependent NF-{kappa}B activity J. Exp. Med., January 3, 2005; 201(1): 105 - 115. [Abstract] [Full Text] [PDF]

				J. Zhou, M. Callapina, G. J. Goodall, and B. Brune Functional Integrity of Nuclear Factor {kappa}B, Phosphatidylinositol 3'-Kinase, and Mitogen-Activated Protein Kinase Signaling Allows Tumor Necrosis Factor {alpha}-Evoked Bcl-2 Expression to Provoke Internal Ribosome Entry Site-Dependent Translation of Hypoxia-Inducible Factor 1{alpha} Cancer Res., December 15, 2004; 64(24): 9041 - 9048. [Abstract] [Full Text] [PDF]

				L. Tacchini, C. De Ponti, E. Matteucci, R. Follis, and M.A. Desiderio Hepatocyte growth factor-activated NF-{kappa}B regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines Carcinogenesis, November 1, 2004; 25(11): 2089 - 2100. [Abstract] [Full Text] [PDF]

				M. J. Velardo, C. Burger, P. R. Williams, H. V. Baker, M. C. Lopez, T. H. Mareci, T. E. White, N. Muzyczka, and P. J. Reier Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord J. Neurosci., September 29, 2004; 24(39): 8562 - 8576. [Abstract] [Full Text] [PDF]

				J. Zhou, T. Schmid, R. Frank, and B. Brune PI3K/Akt Is Required for Heat Shock Proteins to Protect Hypoxia-inducible Factor 1{alpha} from pVHL-independent Degradation J. Biol. Chem., April 2, 2004; 279(14): 13506 - 13513. [Abstract] [Full Text] [PDF]