The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Heme Oxygenase-1 Protein Localizes to the Nucleus and Activates Transcription Factors Important in Oxidative Stress
Open accessAbstract
Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is an integral membrane protein of the smooth endoplasmic reticulum. However, we detected an HO-1 immunoreactive signal in the nucleus of cultured cells after exposure to hypoxia and heme or heme/hemopexin. Under these conditions, a faster migrating HO-1 immunoreactive band was enriched in nuclear extracts, suggesting that HO-1 was cleaved to allow nuclear entry. This was confirmed by the absence of immunoreactive signal with an antibody against the C terminus and the lack of a C-terminal sequence by gas chromatographymass spectrometry. Incubation with leptomycin B prior to hypoxia abolished nuclear HO-1 and the faster migrating band on Western analysis, suggesting that this process was facilitated by CRM1. Furthermore, preincubation with a cysteine protease inhibitor prevented nuclear entry of green fluorescent protein-labeled HO-1, demonstrating that protease-mediated C-terminal cleavage was also necessary for nuclear transport of HO-1. Nuclear localization was also associated with reduction of HO activity. HO-1 protein, whether it was enzymatically active or not, mediated activation of oxidant-responsive transcription factors, including activator protein-1. Nevertheless, nuclear HO-1 protected cells against hydrogen peroxide-mediated injury equally as well as cytoplasmic HO-1. We speculate that nuclear localization of HO-1 protein may serve to up-regulate genes that promote cytoprotection against oxidative stress.
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Cited by
Mechanisms of Cell Protection by Heme Oxygenase-1
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RONS and Oxidative Stress: An Overview of Basic Concepts
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Metadata
- Authors
- Lin, Q., Weis, S., Yang, G., Weng, Y.-H., Helston, R., Rish, K., Smith, A., Bordner, J., Polte, T., Gaunitz, F., & Dennery, P. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 282
- Issue
- 28
- Pages
- 20621-20633
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2040583506
- Cited by
- 416
- References
- 58
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by/4.0/ (vor, 4861 d)
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- Lin, Q., Weis, S., Yang, G., Weng, Y.-H., Helston, R., Rish, K., Smith, A., Bordner, J., Polte, T., Gaunitz, F., & Dennery, P. A. (2007). Heme Oxygenase-1 Protein Localizes to the Nucleus and Activates Transcription Factors Important in Oxidative Stress. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m607954200
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