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Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress.

Authors: Lin, Q  Weis, S  Yang, G  Weng, YH  Helston, R  Rish, K  Smith, A  Bordner, J  Polte, T  Gaunitz, F  Dennery, PA 
Citation: Lin Q, etal., J Biol Chem. 2007 Jul 13;282(28):20621-33. Epub 2007 Apr 12.
Pubmed: (View Article at PubMed) PMID:17430897
DOI: Full-text: DOI:10.1074/jbc.M607954200

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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CRRD Object Information
CRRD ID: 8553479
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.