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Abstract:

The Drosophila HIFα homologue, Sima, is localized mainly in the cytoplasm in normoxia and accumulates in the nucleus upon hypoxic exposure. We have characterized the mechanism governing Sima oxygen-dependent subcellular localization and found that Sima shuttles continuously between the nucleus and the cytoplasm. We have previously shown that nuclear import depends on an atypical bipartite nuclear localization signal mapping next to the C-terminus of the protein. We show here that nuclear export is mediated in part by a CRM1-dependent nuclear export signal localized in the oxygen-dependent degradation domain (ODDD). CRM1-dependent nuclear export requires both oxygen-dependent hydroxylation of a specific prolyl residue (Pro850) in the ODDD, and the activity of the von Hippel Lindau tumor suppressor factor. At high oxygen tension rapid nuclear export of Sima occurs, whereas in hypoxia, Sima nuclear export is largely inhibited. HIFα/Sima nucleo-cytoplasmic localization is the result of a dynamic equilibrium between nuclear import and nuclear export, and nuclear export is modulated by oxygen tension. © 2009 by The American Society for Cell Biology.

Registro:

Documento: Artículo
Título:Central role of the oxygen-dependent degradation domain of Drosophila HIFα/Sima in oxygen-dependent nuclear export
Autor:Irisarri, M.; Lavista-Llanos, S.; Romero, N.M.; Centanin, L.; Dekanty, A.; Wappner, P.
Filiación:Instituto Leloir and FCEyN, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas Y Técnicas, 1405 Buenos Aires, Argentina
Palabras clave:Drosophila protein; exportin 1; hypoxia inducible factor 1alpha; oxygen; Sima protein; unclassified drug; animal cell; article; cell hypoxia; cell nucleus; cellular distribution; controlled study; cytoplasm; Drosophila; hydroxylation; nonhuman; nuclear export signal; nuclear import; oxygen tension; priority journal; protein degradation; protein domain; protein localization; protein transport; Active Transport, Cell Nucleus; Amino Acid Sequence; Animals; Animals, Genetically Modified; DNA-Binding Proteins; Drosophila melanogaster; Drosophila Proteins; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Sequence Data; Nuclear Export Signals; Oxygen; Procollagen-Proline Dioxygenase; Recombinant Fusion Proteins; Transgenes; Von Hippel-Lindau Tumor Suppressor Protein
Año:2009
Volumen:20
Número:17
Página de inicio:3878
Página de fin:3887
DOI: http://dx.doi.org/10.1091/mbc.E09-01-0038
Título revista:Molecular Biology of the Cell
Título revista abreviado:Mol. Biol. Cell
ISSN:10591524
CODEN:MBCEE
CAS:oxygen, 7782-44-7; DNA-Binding Proteins; Drosophila Proteins; Hypoxia-Inducible Factor 1, alpha Subunit; Nuclear Export Signals; Oxygen, 7782-44-7; Procollagen-Proline Dioxygenase, 1.14.11.2; Recombinant Fusion Proteins; Sima protein, Drosophila; Von Hippel-Lindau Tumor Suppressor Protein, 6.3.2.19
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10591524_v20_n17_p3878_Irisarri

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Citas:

---------- APA ----------
Irisarri, M., Lavista-Llanos, S., Romero, N.M., Centanin, L., Dekanty, A. & Wappner, P. (2009) . Central role of the oxygen-dependent degradation domain of Drosophila HIFα/Sima in oxygen-dependent nuclear export. Molecular Biology of the Cell, 20(17), 3878-3887.
http://dx.doi.org/10.1091/mbc.E09-01-0038
---------- CHICAGO ----------
Irisarri, M., Lavista-Llanos, S., Romero, N.M., Centanin, L., Dekanty, A., Wappner, P. "Central role of the oxygen-dependent degradation domain of Drosophila HIFα/Sima in oxygen-dependent nuclear export" . Molecular Biology of the Cell 20, no. 17 (2009) : 3878-3887.
http://dx.doi.org/10.1091/mbc.E09-01-0038
---------- MLA ----------
Irisarri, M., Lavista-Llanos, S., Romero, N.M., Centanin, L., Dekanty, A., Wappner, P. "Central role of the oxygen-dependent degradation domain of Drosophila HIFα/Sima in oxygen-dependent nuclear export" . Molecular Biology of the Cell, vol. 20, no. 17, 2009, pp. 3878-3887.
http://dx.doi.org/10.1091/mbc.E09-01-0038
---------- VANCOUVER ----------
Irisarri, M., Lavista-Llanos, S., Romero, N.M., Centanin, L., Dekanty, A., Wappner, P. Central role of the oxygen-dependent degradation domain of Drosophila HIFα/Sima in oxygen-dependent nuclear export. Mol. Biol. Cell. 2009;20(17):3878-3887.
http://dx.doi.org/10.1091/mbc.E09-01-0038