Kapitulnik Jaime, Maines Mahin D
Department of Pharmacology, the David R. Bloom Center for Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem, Israel.
Trends Pharmacol Sci. 2009 Mar;30(3):129-37. doi: 10.1016/j.tips.2008.12.003. Epub 2009 Feb 11.
Degradation of heme requires its conversion to biliverdin (BV) by heme oxygenase, followed by reduction of BV to the free-radical quencher bilirubin (BR) by biliverdin reductase (BVR). It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser/Thr and Tyr) upstream activator of the insulin/insulin growth factor-1 (IGF-1) and mitogen-activated protein kinase (MAPK) signaling pathways. hBVR is also a basic-leucine-zipper (bZip) DNA/chromatin-binding transcription factor, an activator and anchor protein for translocation of protein kinase C betaII and zeta isozymes within cell compartments, and a kinase kinase for their activation. hBVR is essential for MAPK-extracellular signal-regulated kinase (ERK)1/2 (MEK)-eukaryotic-like protein kinase (Elk) signaling and has been identified as the cytoplasm-nuclear heme transporter of ERK1/2 and hematin, the key components of stress-responsive gene expression. Here, we discuss the recently uncovered functions of hBVR in cell signaling and regulation of gene expression, and the role of BR in cellular signaling, cytoprotection and cytotoxicity.
血红素的降解需要通过血红素加氧酶将其转化为胆绿素（BV），随后通过胆绿素还原酶（BVR）将BV还原为自由基淬灭剂胆红素（BR）。现在人们认识到，人BVR（hBVR）是胰岛素/胰岛素生长因子-1（IGF-1）和丝裂原活化蛋白激酶（MAPK）信号通路的双特异性激酶（丝氨酸/苏氨酸和酪氨酸）上游激活剂。hBVR还是一种碱性亮氨酸拉链（bZip）DNA/染色质结合转录因子，是蛋白激酶CβII和ζ同工酶在细胞区室内易位的激活剂和锚定蛋白，也是其激活的激酶激酶。hBVR对MAPK-细胞外信号调节激酶（ERK）1/2（MEK）-真核样蛋白激酶（Elk）信号传导至关重要，并且已被确定为ERK1/2和高铁血红素的细胞质-核血红素转运体，而ERK1/2和高铁血红素是应激反应基因表达的关键成分。在这里，我们讨论hBVR在细胞信号传导和基因表达调控方面最近发现的功能，以及BR在细胞信号传导、细胞保护和细胞毒性中的作用。
