Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1074/jbc.M607954200 |
| Titel (primär) | Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress |
| Autor | Lin, Q.; Weis, S.; Yang, G.; Weng, Y.H.; Helston, R.; Rish, K.; Smith, A.; Bordner, J.; Polte, T.; Gaunitz, F.; Dennery, P.A. |
| Quelle | Journal of Biological Chemistry |
| Erscheinungsjahr | 2007 |
| Department | IMMU |
| Band/Volume | 282 |
| Heft | 28 |
| Seite von | 20621 |
| Seite bis | 20633 |
| Sprache | englisch |
| Abstract | 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 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 GC-MS. Incubation with Leptomycin B (LMB) 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 GFP-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 AP-1. Nevertheless, nuclear HO-1 equally protected cells against hydrogen peroxide mediated injury 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. |
| 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 J. Biol. Chem. 282 (28), 20621 - 20633 10.1074/jbc.M607954200 |
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