FIH-1, faktori joka estää HIF-hydroksyloitumista .

In addition to PHD, there are other factors regulating the HIF stability/activity. Factor-inhibiting-HIF (FIH) hydroxylates regulates HIF activation via controlling CBP/p300 recruitment. The phosphoinositide 3-kinase (PI3K)/Akt pathway and the protein kinase C signaling have also been implicated in the regulation of HIF-α. Whether these pathways can be a good target for therapeutic approaches is a future subject to be pursed.
 https://www.ahajournals.org/doi/10.1161/ATVBAHA.107.148551

Preferred Names

hypoxia-inducible factor 1-alpha inhibitor

Names

FIH-1

factor inhibiting HIF-1

factor inhibiting HIF1

hypoxia inducible factor 1 alpha subunit inhibitor

hypoxia-inducible factor asparagine hydroxylase

peptide-aspartate beta-dioxygenase

Conserved Domains (1) summary

pfam13621
Location:53 → 297

Cupin_8; Cupin-like domain. This cupin like domain shares similarity to the JmjC domain.

Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5367-72.

Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.

Freedman SJ¹, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ.

1Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.Abstract

Adaptation to hypoxia is mediated by transactivation of hypoxia-responsive genes by hypoxia-inducible factor-1 (HIF-1) in complex with the CBP and p300 transcriptional coactivators.
We report the solution structure of the cysteine/histidine-rich 1 (CH1) domain of p300 bound to the C-terminal transactivation domain of HIF-1 alpha.
 CH1 has a triangular geometry composed of four alpha-helices with three intervening Zn(2+)-coordinating centers.
 CH1 serves as a scaffold for folding of the HIF-1 alpha C-terminal transactivation domain, which forms a vise-like clamp on the CH1 domain that is stabilized by extensive hydrophobic and polar interactions. The structure reveals the mechanism of specific recognition of p300 by HIF-1 alpha, and shows how HIF-1 alpha transactivation is regulated by asparagine hydroxylation.

PMID:

11959990

PMCID:

PMC122775

DOI:

10.1073/pnas.082117899

[Indexed for MEDLINE]

Free PMC Article