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Activation and function of hypoxia inducible transcription factors

Mammalian organisms show a broad range of respons to lowered oxygen levels induced by hypoxia or ischemia. Highly involved in the adaption of affected cells or tissues to insufficient oxygen supply are the members of the basic helix-loop-helix PAS (Per-Arnt-Sim) domain transcription factor family called hypoxia-inducible factors (HIF).
For many years HIF-1 was the only known member of this specific family of heterodimeric transcription factors. The mechanism of hypoxia-dependent activation and function of the HIF-1 complex (HIF-1alpha/ARNT), is currently poorly understood. The same is true for HIF-2a and HIF-2. Although the 2a subunit of the HIF transcription factor family has been shown to be mainly expressed in highly vascularized organs and was found to be over-expressed in various cancer cell lines, its specific function remains unclear. The goal of this project is to gain more insight into the mechanism of activation and stabilization of HIFs and to examine their role in tumor angiogenesis in more detail.
Project leader
Dadak Agnes
Type of Research
Basic research
Vetmed Research Units
Institute of Pharmacology and Toxicology
Projekt partner
University of California, Department of Biology
Funded by
UCSD, Department of Biology, Dr., La Jolla, 9500 Gilman CA 92093-0346, United States (USA)
5 Publications

Tamura, K; Sudo, T; Senftleben, U; Dadak, AM; Johnson, R; Karin, M (2000): Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis. Cell. 2000; 102(2):221-231

Dadak, A (2005): Aktivierung und Funktion der Hypoxie-induzierbaren Transkriptionsfaktoren (HIFs). 15. Symposium der deutschsprachigen Veterinärpharmakologen und -toxikologen, Wien, Austria, 29./30. 09. 2005. 15. Symposium der deutschsprachigen Veterinärpharmakologen und -toxikologen, Wien, 29./30. 09. 2005.

Huang, Y; Hickey, RP; Yeh, JL; Liu, D; Dadak, A; Young, LH; Johnson, RS; Giordano, FJ (2004): Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. Faseb J (18), 10 1138-1140.
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Park, SK; Dadak, AM; Haase, VH; Fontana, L; Giaccia, AJ; Johnson, RS (2003): Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol Cell Biol (23), 14 4959-4971.
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Dadak, AM; Park, SK; Johnson, RS (2002): HIF-2a is not a HIF-1a redundant factor for transcriptional activation of HIF-1 target genes under hypoxic conditions. 136-136.-The 2nd International Conference on Tumor Microenvironment: Progression, Therapy and Prevention; June 25-29, 2002; Baden, Austria.

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