Nuclear-cytoplasmatic shuttling of proteins in control of cellular oxygen sensing
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| 024 | 7 | 0 | |a 10.1007/s00109-015-1276-0 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-015-1276-0 | ||
| 245 | 0 | 0 | |a Nuclear-cytoplasmatic shuttling of proteins in control of cellular oxygen sensing |h [Elektronische Daten] |c [Reinhard Depping, Wolfgang Jelkmann, Friederike Kosyna] |
| 520 | 3 | |a In order to pass through the nuclear pore complex, proteins larger than ∼40kDa require specific nuclear transport receptors. Defects in nuclear-cytoplasmatic transport affect fundamental processes such as development, inflammation and oxygen sensing. The transcriptional response to O2 deficiency is controlled by hypoxia-inducible factors (HIFs). These are heterodimeric transcription factors of each ∼100-120kDa proteins, consisting of one out of three different O2-labile α subunits (primarily HIF-1α) and a more constitutive 1β subunit. In the presence of O2, the α subunits are hydroxylated by specific prolyl-4-hydroxylase domain proteins (PHD1, PHD2, and PHD3) and an asparaginyl hydroxylase (factor inhibiting HIF-1, FIH-1). The prolyl hydroxylation causes recognition by von Hippel-Lindau tumor suppressor protein (pVHL), ubiquitination, and proteasomal degradation. The activity of the oxygen sensing machinery depends on dynamic intracellular trafficking. Nuclear import of HIF-1α and HIF-1β is mainly mediated by importins α and β (α/β). HIF-1α can shuttle between nucleus and cytoplasm, while HIF-1β is permanently inside the nucleus. pVHL is localized to both compartments. Nuclear import of PHD1 relies on a nuclear localization signal (NLS) and uses the classical import pathway involving importin α/β receptors. PHD2 shows an atypical NLS, and its nuclear import does not occur via the classical pathway. PHD2-mediated hydroxylation of HIF-1α occurs predominantly in the cell nucleus. Nuclear export of PHD2 involves a nuclear export signal (NES) in the N-terminus and depends on the export receptor chromosome region maintenance 1 (CRM1). Nuclear import of PHD3 is mediated by importin α/β receptors and depends on a non-classical NLS. Specific modification of the nuclear translocation of the three PHD isoforms could provide a promising strategy for the development of new therapeutic substances to tackle major diseases. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Hypoxia-inducible factors (HIF) |2 nationallicence | |
| 690 | 7 | |a Importin |2 nationallicence | |
| 690 | 7 | |a Nuclear export |2 nationallicence | |
| 690 | 7 | |a Nuclear import |2 nationallicence | |
| 690 | 7 | |a HIF prolyl hydroxylases (PHD) |2 nationallicence | |
| 700 | 1 | |a Depping |D Reinhard |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | |
| 700 | 1 | |a Jelkmann |D Wolfgang |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | |
| 700 | 1 | |a Kosyna |D Friederike |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/6(2015-06-01), 599-608 |x 0946-2716 |q 93:6<599 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-015-1276-0 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a review-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-015-1276-0 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Depping |D Reinhard |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jelkmann |D Wolfgang |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kosyna |D Friederike |u Institute of Physiology, Centre for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/6(2015-06-01), 599-608 |x 0946-2716 |q 93:6<599 |1 2015 |2 93 |o 109 | ||