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:
CreatorsEmailORCIDORCID Put Code
Gimm, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiese, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teschemacher, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deggerich, AnkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoedel, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knaup, Karl X.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hackenbeck, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hellerbrand, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amann, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesener, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckardt, Kai-UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warnecke, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
RENAL-CELL CARCINOMA; DIFFERENTIATION-RELATED PROTEIN; FACTOR (HIF)-1-ALPHA; TRANSCRIPTION FACTORS; INSULIN-RESISTANCE; RNA INTERFERENCE; LIVER-CELLS; DNA-BINDING; FOAM CELLS; EXPRESSIONMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49329

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item