The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1 α and Mediates Its Destabilization in a VHL-Independent Manner
Open accessAbstract
Hypoxia-inducible transcription factor 1alpha (HIF-1alpha) is a key player in the response to hypoxia. Additionally, HIF-1alpha responds to growth factors and hormones which can act via protein kinase B (Akt). However, HIF-1alpha is not a direct substrate for this kinase. Therefore, we investigated whether the protein kinase B target glycogen synthase kinase 3 (GSK-3) may have an impact on HIF-1alpha. We found that the inhibition or depletion of GSK-3 induced HIF-1alpha whereas the overexpression of GSK-3beta reduced HIF-1alpha. These effects were mediated via three amino acid residues in the oxygen-dependent degradation domain of HIF-1alpha. In addition, mutation analyses and experiments with von Hippel-Lindau (VHL)-defective cells indicated that GSK-3 mediates HIF-1alpha degradation in a VHL-independent manner. In line with these observations, the inhibition of the proteasome reversed the GSK-3 effects, indicating that GSK-3 may target HIF-1alpha to the proteasome by phosphorylation. Thus, the direct regulation of HIF-1alpha stability by GSK-3 may influence physiological processes or pathophysiological situations such as metabolic diseases or tumors.
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Cites
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“A major pathway appears to be the posttranslational modification of HIF-1 via the oxygen-dependent hydroxylation ( 29 , 30) of two proline residues (P402 and P564) within the O2-dependent degradation domain (ODD), which overlaps with an N-terminal transactivation domain (TAD-N), and that of an asparagine residue (N803…”
BackgroundHIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385
Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256 · cited 2×
“Indeed, some investigations pointed to a role for mTOR (1, 40 , 65) in the regulation of HIF-1 protein levels, and others showed the involvement of GSK-3 (10, 46, 59).”
BackgroundWenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135
Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
Cited by
GSK-3: Functional Insights from Cell Biology and Animal Models
Kaidanovich-Beilin, O., & Woodgett, J. R. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00040 · Cited by 485
HIF-1 regulation: not so easy come, easy go
Koh, M. Y., Spivak-Kroizman, T. R., & Powis, G. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.08.002 · Cited by 339
Hypoxia-inducible factors and the regulation of lipid metabolism
Mylonis, I., Simos, G., & Paraskeva, E. (2019) · Cells · doi:10.3390/cells8030214 · Cited by 316
Kietzmann, T., Mennerich, D., & Dimova, E. Y. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00011 · Cited by 176
Self-citationEvolutionary Conserved Regulation of HIF-1β by NF-κB
van Uden, P., Kenneth, N. S., Webster, R., Müller, H. A., Mudie, S., & Rocha, S. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001285 · Cited by 163
Metadata
- Authors
- Flügel, D., Görlach, A., Michiels, C., & Kietzmann, T.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-05-01
- Volume
- 27
- Issue
- 9
- Pages
- 3253-3265
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2126244927
- Cited by
- 258
- References
- 9
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Flügel, D., Görlach, A., Michiels, C., & Kietzmann, T. (2007). Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1 α and Mediates Its Destabilization in a VHL-Independent Manner. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.00015-07
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