CYP1B1: A Unique Gene with Unique Characteristics

Abstract

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.

Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications

“…They metabolize tobacco constituents—benzo(a)pyrene and nicotine, respectively—and are responsible for smoking-mediated carcinogenesis as well as liver toxicity [31,32]. In addition to cancers, CYP1B1 is known to be induced under many disease conditions and has been implicated as an important biological marker for the predictive diagnosis of developmental disorders [33]. Plasma exosomes containing CYP2A6 may be used as biological markers for nicotine dependence, because it is known to be induced by nicotine and rapidly metabolizes nicotine in the liver [33].…”

“…In addition to cancers, CYP1B1 is known to be induced under many disease conditions and has been implicated as an important biological marker for the predictive diagnosis of developmental disorders [33]. Plasma exosomes containing CYP2A6 may be used as biological markers for nicotine dependence, because it is known to be induced by nicotine and rapidly metabolizes nicotine in the liver [33]. Among the important drug-metabolic CYP enzymes, CYP3A4 showed detectable levels of both mRNA and proteins, as well as H 2 O 2 -dependent enzyme activity.…”

Alternative Splicing in the Cytochrome P450 Superfamily Expands Protein Diversity to Augment Gene Function and Redirect Human Drug Metabolism

“…In this regard, the most well studied splice variants of CYP1B1 all represent severe truncations or deletion mutants, not exon skipping (Tanwar et al, 2009), and CYP1B1 retains an unusual, elongated C-terminus, further distinguishing it from other human P450 forms. The CYP1B1 gene is also uniquely located on chromosome 2 at locus 2p21-22, which in humans is derived from an ancient fusion of chimpanzee chromosomes 2a and 2b (Faiq et al, 2014). It is difficult to speculate why the CYP1B1 gene is organized so differently from closely related CYP1A genes located on chromosome 15.…”

Identification of Candidate Target <i>Cyp</i> Genes for microRNAs Whose Expression Is Altered by PCN and TCPOBOP, Representative Ligands of PXR and CAR

“…Our study demonstrated for the first time that Cyp2c38 is downregulated by PCN or TCPOBOP treatment and suggests that miR-26b-3p may play a role in Cyp2c38's regulation. In addition, our results showed that the mRNA expression of Cyp1b1, which is known to metabolize several pro-carcinogens, 20) was increased in response to PCN. This result is consistent with recent reports from two separate groups indicating that PXR activation up-regulates Cyp1b1's expression in vascular endothelial cells 21) or skin 22) ; however, the induction mechanism was unclear.…”