Florczyk Urszula M, Jozkowicz Alicja, Dulak Jozef
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, Poland.
Pharmacol Rep. 2008 Jan-Feb;60(1):38-48.
Biliverdin reductase (BVR) was known for a long time solely as an enzyme converting biliverdin to bilirubin, the major physiological antioxidant. Recent years revealed unique features of this protein which are not related to its reductase activity. The most intriguing and surprising finding is its dual-specificity kinase character. As such serine/threonine/tyrosine kinase BVR is involved in regulation of glucose metabolism or in control of cell growth and apoptosis. In consequence, it may play a role in pathogenesis of many diseases, such as diabetes or cancers. Moreover, in the nucleus BVR, being a leucine zipper-like DNA binding protein, can act as a transcription factor for activator protein 1 (AP-1)-regulated genes. It has been shown that BVR modulates ATF-2 and HO-1 expression, what suggests its potential role in control of AP-1 and cAMP-regulated genes. In conclusion, BVR together with its substrate, biliverdin, and product, bilirubin, are revealed to be important players in cellular signal transduction pathways, gene expression and oxidative response. These features make BVR unusually interesting and unique among all enzymes characterized to date.
长期以来，胆绿素还原酶（BVR）仅被认为是一种将胆绿素转化为胆红素（主要的生理抗氧化剂）的酶。近年来发现了这种蛋白质的一些独特特性，这些特性与其还原酶活性无关。最引人入胜且令人惊讶的发现是其双特异性激酶特性。作为丝氨酸/苏氨酸/酪氨酸激酶，BVR参与葡萄糖代谢的调节或细胞生长及凋亡的控制。因此，它可能在许多疾病（如糖尿病或癌症）的发病机制中发挥作用。此外，在细胞核中，BVR作为一种类似亮氨酸拉链的DNA结合蛋白，可作为激活蛋白1（AP-1）调控基因的转录因子。研究表明，BVR可调节ATF-2和HO-1的表达，这表明其在控制AP-1和cAMP调控基因方面具有潜在作用。总之，BVR及其底物胆绿素和产物胆红素在细胞信号转导途径、基因表达和氧化反应中都是重要参与者。这些特性使BVR在迄今为止所描述的所有酶中显得格外有趣和独特。
