TY - JOUR
T1 - Cellular oxygen sensing
T2 - Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2
AU - Steinhoff, Amrei
AU - Pientka, Friederike Katharina
AU - Möckel, Sylvia
AU - Kettelhake, Antje
AU - Hartmann, Enno
AU - Köhler, Matthias
AU - Depping, Reinhard
PY - 2009/10/2
Y1 - 2009/10/2
N2 - Hypoxia-inducible factors are crucial in the regulatory process of oxygen homeostasis of vertebrate cells. Inhibition of prolyl hydroxylation of HIF-α subunits by prolyl-hydroxylases (PHD1, PHD2 and PHD3) leads to transcription of a greater number of hypoxia responsive genes. We have investigated the subcellular distribution and the molecular mechanisms regulating the intracellular allocation of PHD1 and PHD2. As reported earlier we find PHD1 located exclusively in the nucleus. We demonstrate that nuclear import of PHD1 occurs importin α/β dependently and relies on a nuclear localisation signal (NLS). By contrast PHD2 is cycling between nucleus and cytoplasm, and nuclear import seems to be independent of "classical" importin α/β receptors. Furthermore, we reveal that the exit of PHD2 from the nucleus requires CRM1 and the N-terminal 100 amino acids of the protein. Our findings provide new insights into the mechanisms of the regulation of the oxygen sensor cascade of PHDs in different cellular compartments.
AB - Hypoxia-inducible factors are crucial in the regulatory process of oxygen homeostasis of vertebrate cells. Inhibition of prolyl hydroxylation of HIF-α subunits by prolyl-hydroxylases (PHD1, PHD2 and PHD3) leads to transcription of a greater number of hypoxia responsive genes. We have investigated the subcellular distribution and the molecular mechanisms regulating the intracellular allocation of PHD1 and PHD2. As reported earlier we find PHD1 located exclusively in the nucleus. We demonstrate that nuclear import of PHD1 occurs importin α/β dependently and relies on a nuclear localisation signal (NLS). By contrast PHD2 is cycling between nucleus and cytoplasm, and nuclear import seems to be independent of "classical" importin α/β receptors. Furthermore, we reveal that the exit of PHD2 from the nucleus requires CRM1 and the N-terminal 100 amino acids of the protein. Our findings provide new insights into the mechanisms of the regulation of the oxygen sensor cascade of PHDs in different cellular compartments.
UR - http://www.scopus.com/inward/record.url?scp=68749094122&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.07.090
DO - 10.1016/j.bbrc.2009.07.090
M3 - Journal articles
C2 - 19631610
AN - SCOPUS:68749094122
SN - 0006-291X
VL - 387
SP - 705
EP - 711
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -