Medical University of Lodz, Department of Analytical Chemistry, Muszynskiego 1, 90-151 Lodz, Poland.
Z Naturforsch C J Biosci. 2011 Jan-Feb;66(1-2):73-82.
WWOX is a tumour suppressor gene that spans the common fragile site FRA16D. Analysis of the WWOX expression pattern in normal human tissues showed the highest expression in testis, prostate, and ovary. Its altered expression has been demonstrated in different tissues and tumour types. The WWOX gene encodes a 414-amino acids protein, which is the first discovered protein with a short-chain dehydrogenase/reductase (SDR) central domain and two WW domains at the NH2 terminus. Due to its potential role in sex-steroid metabolism, using two bacterial expression systems, we have cloned WWOX fusion proteins showing oxidoreductase activity in a crude extract, defined a course of enzymatic reactions for selected steroid substrates, and determined related Km values. Our results show that the SDR domain of the WWOX protein has dehydrogenase activity and is reactive both in the presence of NAD+ and NADP+ for all examined steroid substrates. On the other hand, with the same substrates and reduced cofactors (NADH and NADPH) reduction activity was not observed.
WWOX 是一个肿瘤抑制基因，跨越常见的脆性部位 FRA16D。对正常人体组织中 WWOX 表达模式的分析表明，其在睾丸、前列腺和卵巢中的表达最高。其表达的改变已在不同的组织和肿瘤类型中得到证实。WWOX 基因编码一个 414 个氨基酸的蛋白质，这是第一个发现具有短链脱氢酶/还原酶 (SDR) 中心结构域和 NH2 末端两个 WW 结构域的蛋白质。由于其在性激素代谢中的潜在作用，我们使用两种细菌表达系统克隆了 WWOX 融合蛋白，在粗提物中显示出氧化还原酶活性，确定了选定类固醇底物的酶促反应过程，并确定了相关的 Km 值。我们的结果表明，WWOX 蛋白的 SDR 结构域具有脱氢酶活性，并且对所有检查的类固醇底物都具有 NAD+和 NADP+存在时的反应性。另一方面，用相同的底物和还原辅酶 (NADH 和 NADPH) 没有观察到还原活性。
