Universität zu Köln

Gimm, Tina, Wiese, Melanie, Teschemacher, Barbara, Deggerich, Anke, Schoedel, Johannes, Knaup, Karl X., Hackenbeck, Thomas, Hellerbrand, Claus, Amann, Kerstin, Wiesener, Michael S., Hoening, Stefan, Eckardt, Kai-Uwe and Warnecke, Christina (2010). Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. Faseb J., 24 (11). S. 4443 - 4459. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

Full text not available from this repository.

Abstract

Hypoxia-inducible protein 2 (HIG2) has been implicated in canonical Wnt signaling, both as target and activator. The potential link between hypoxia and an oncogenic signaling pathway might play a pivotal role in renal clear-cell carcinoma characterized by constitutive activation of hypoxia-inducible factors (HIFs), and hence prompted us to analyze HIG2 regulation and function in detail. HIG2 was up-regulated by hypoxia and HIF inducers in all cell types and mouse organs investigated and abundantly expressed in renal clear-cell carcinomas. Promoter analyses, gel shifts, and siRNA studies revealed that HIG2 is a direct and specific target of HIF-1, but not responsive to HIF-2. Surprisingly, HIG2 was not secreted, and HIG2 overexpression neither stimulated proliferation nor activated Wnt signaling. Instead, we show that HIG2 decorates the hemimembrane of lipid droplets, whose number and size increase on hypoxic inhibition of fatty acid beta-oxidation, and colocalizes with the lipid droplet proteins adipophilin and TIP47. Normoxic overexpression of HIG2 was sufficient to increase neutral lipid deposition in HeLa cells and stimulated cytokine expression. HIG2 could be detected in atherosclerotic arteries and fatty liver disease, suggesting that this ubiquitously inducible HIF-1 target gene may play an important functional role in diseases associated with pathological lipid accumulation.-Gimm, T., Wiese, M., Teschemacher, B., Deggerich, A., Schodel, J., Knaup, K. X., Hackenbeck, T., Hellerbrand, C., Amann, K., Wiesener, M. S., Honing, S., Eckardt, K.-U., Warnecke, C. Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J. 24, 4443-4458 (2010). www.fasebj.org

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gimm, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiese, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Teschemacher, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Deggerich, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoedel, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Knaup, Karl X. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackenbeck, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellerbrand, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Amann, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesener, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoening, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckardt, Kai-Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnecke, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-493295
DOI:	10.1096/fj.10-159806
Journal or Publication Title:	Faseb J.
Volume:	24
Number:	11
Page Range:	S. 4443 - 4459
Date:	2010
Publisher:	FEDERATION AMER SOC EXP BIOL
Place of Publication:	BETHESDA
ISSN:	1530-6860
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RENAL-CELL CARCINOMA; DIFFERENTIATION-RELATED PROTEIN; FACTOR (HIF)-1-ALPHA; TRANSCRIPTION FACTORS; INSULIN-RESISTANCE; RNA INTERFERENCE; LIVER-CELLS; DNA-BINDING; FOAM CELLS; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49329