Faiq Muneeb A, Dada Rima, Sharma Reetika, Saluja Daman, Dada Tanuj
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Curr Drug Metab. 2014;15(9):893-914. doi: 10.2174/1389200216666150206130058.
CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.
CYP1B1是一种最近被描述的二噁英诱导氧化还原酶,是细胞色素P450超家族的成员,参与雌二醇、视黄醇、苯并[a]芘、他莫昔芬、褪黑素、甾醇等的代谢。它在众多生理过程中发挥重要作用,并在许多组织和解剖部位以mRNA水平表达。CYP1B1与多种疾病有关。对近期研究的分析表明,CYP1B1可作为一种通用/理想的癌症标志物以及预测诊断的候选基因。关于CYP1B1某些方面的文献很多,但尚未得到解释、讨论和深入思考。本分析将CYP1B1视为一种具有某些独特特征的特殊基因,如其染色体定位、基因结构和组织的独特性、参与发育重要疾病、组织特异性,不仅是表达,还有剪接,因其参与细胞代谢的关键方面而具有作为通用癌症标志物的潜力、在各种疾病诊断和预测诊断中的应用以及CYP1B1 mRNA除常规翻译外的重要性和功能。此外,CYP1B1在异源表达系统中很难表达,从而阻碍了其功能研究。在这里,我们结合自身经验回顾和分析CYP1B1的这些特殊和惊人的特征,以便更好地洞察其在健康和疾病中的分子生物学。这可能有助于进一步了解CYP1B1介导疾病的病因发病机制,为更好的研究策略和改善临床管理铺平道路。