Heme Oxygenase-1 (HO-1) is a type II detoxifying enzyme that catalyzes the rate-limiting step in heme degradation leading to the formation of equimolar quantities of carbon monoxide (CO), free iron and biliverdin. HO-1 was originally shown to localize at the smooth endoplasmic reticulum membrane (sER), although increasing evidence demonstrates that the protein translocates to other subcellular compartments including the nucleus. The nuclear translocation occurs after proteolytic cleavage by proteases including signal peptide peptidase and some cysteine proteases. In addition, nuclear translocation has been demonstrated to be involved in several cellular processes leading to cancer progression, including induction of resistance to therapy and enhanced metastatic activity. In this review, we focus on nuclear HO-1 implication in pathophysiological conditions with special emphasis on malignant processes. We provide a brief background on the current understanding of the mechanisms underlying how HO-1 leaves the sER membrane and migrates to the nucleus, the circumstances under which it does so and, maybe the most important and unknown aspect, what the function of HO-1 in the nucleus is.

中文翻译：

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血红素加氧酶-1在病理生理条件下的核定位：是否解释了癌症的双重作用？

血红素加氧酶-1（HO-1）是II型解毒酶，可催化血红素降解中的限速步骤，导致形成等摩尔量的一氧化碳（CO），游离铁和胆绿素。HO-1最初显示位于平滑内质网膜（sER），尽管越来越多的证据表明HO-1易位至包括核在内的其他亚细胞区室。核易位发生在蛋白酶（包括信号肽肽酶和一些半胱氨酸蛋白酶）进行蛋白水解切割之后。另外，已经证明核易位涉及导致癌症进展的几种细胞过程，包括诱导对治疗的抗性和增强的转移活性。在这篇评论中 我们专注于病理生理条件下的核HO-1的影响，特别强调恶性过程。我们提供了有关HO-1如何离开sER膜并迁移到细胞核的机制的当前背景的简要背景，其在何种情况下以及可能最重要和未知的方面，HO-的功能是什么。在核中是1。