Role of the intracellular localization of HIF-prolyl hydroxylases.

Article Details


Yasumoto K, Kowata Y, Yoshida A, Torii S, Sogawa K

Role of the intracellular localization of HIF-prolyl hydroxylases.

Biochim Biophys Acta. 2009 May;1793(5):792-7. doi: 10.1016/j.bbamcr.2009.01.014. Epub 2009 Feb 5.

PubMed ID
19339211 [ View in PubMed

Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor regulating the response of tumor cells to hypoxia and is comprised of HIF-1alpha and Arnt (HIF-1beta). In mammalian cells, HIF-1 protein levels are regulated by three HIF-prolyl hydroxylases, termed PHD1, PHD2 and PHD3. To assess whether intracellular localization of PHD1 and PHD2 affects the hypoxic response via HIF-1, we investigated the localization signal of PHDs. PHD1 possessed at least one nuclear localization signal (NLS), and PHD2 contained a region as essential for nuclear export in their N-terminal region. Treatment of cells with leptomycin B revealed that PHD2 was able to shuttle between the cytoplasm and the nucleus. Reporter assay indicated that differences in the intracellular distribution of PHD1 did not influence on HIF-1alpha activity. However, a PHD2 mutant lacking the region for nuclear export exhibited significantly reduced effect to HIF-1alpha activity compared to wild-type PHD2, suggesting that the regulation of the intracellular distribution of PHD2 is an effective pathway for the control of the hypoxic response.

DrugBank Data that Cites this Article

NameUniProt ID
Egl nine homolog 2Q96KS0Details
Egl nine homolog 1Q9GZT9Details