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Gene Review

Cyp1b1  -  cytochrome P450, family 1, subfamily b,...

Mus musculus

Synonyms: CP1B, CYPIB1, Cyp1-b1, Cytochrome P450 1B1, Cytochrome P450CMEF, ...
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Disease relevance of Cyp1b1


High impact information on Cyp1b1

  • From the partial sequence of the cDNA identified by this procedure, we propose that P450CMEF is a member of the P450 superfamily, possibly in a subfamily of family 1, that is induced in 10T1/2 cells by DMBA and BA [3].
  • A cytochrome P450-like gene, tentatively named P450CMEF, was amplified by a mixed oligonucleotide-primed amplification of cDNA from C3H mouse embryo fibroblast cells, designated 10T1/2, that had been treated with 7,12-dimethylbenz[a]anthracene (DMBA) or benz[a]anthracene (BA) [3].
  • The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells [4].
  • At the functional level, antibody inhibition studies and product ratios demonstrated that P-4501A1 accounted for only 40% of the total dimethylbenz(a)anthracene-metabolizing activity of BA-induced tumor microsomes, whereas the remaining activity was due to P-450-EF [5].
  • The 3-methylcholanthrene-transformed tumorigenic cell line, MCA-C3H/10T1/2 CL15 (MCA), expresses the novel benz(a)anthracene (BA)-inducible polycyclic aromatic hydrocarbon-metabolizing cytochrome P-450 (P-450-EF) [5].

Biological context of Cyp1b1

  • Real-time reverse transcription-polymerase chain reaction analyses of mouse embryonic fibroblasts showed that the mixtures had an additive effect on the mRNA levels of Cyp1b1, a prototypical phase I detoxification gene, and an AHR-dependent synergistic effect on the corresponding levels of Nqo1, a prototypical phase II gene [6].
  • Expression of Cyp1b1 in the dorso-distal end of the optic cup, from which the ciliary body and iris are derived, correlates with the expression patterns seen in adult tissues and the abnormal development of these structures as part of the glaucoma phenotypes resulting from Cyp1b1 mutations [7].
  • CONCLUSIONS: The spatio-temporal expression patterns observed in this study suggest that during early stages of murine development, Cyp1b1 participates in establishment and/or maintenance of polarity along the axes of embryonic development [7].
  • Cells treated with medium conditioned by several days of cell growth supported increases in the dimethylbenz(a)anthracene induction of mRNA expression of a new mouse cytochrome P450 gene designated Cyp1b1, aryl hydrocarbon hydroxylase activity, cytotoxicity, and the frequency of neoplastic transformation [8].
  • This equal stimulation of P450EF by BA and TCDD is consistent with transcriptional activation of the gene by the AhR [9].

Anatomical context of Cyp1b1

  • In the forelimb bud Cyp1b1 expression was localized posteriorly [7].
  • RESULTS: During early stages of murine development Cyp1b1 mRNA was detected in the developing eye, hindbrain, branchial arches, forelimb bud, ligaments supporting the liver primordium and developing kidney [7].
  • CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract [10].
  • Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice [10].
  • Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P < 0.05) [10].

Associations of Cyp1b1 with chemical compounds

  • These results show that Cyp1b1 mRNA expression is less inducible by TCDD than Cyp1a1 [11].
  • The major metabolites of arachidonic acid by Cyp1b1 were EETs (50%) and midchain HETEs (37%) [12].
  • During a 6-hr inhibition of protein synthesis with cycloheximide, both total P450EF and functional cytochrome, measured by polycyclic aromatic hydrocarbon metabolism, decreased by 60% in uninduced and TCDD-induced transformed 10T1/2 cells [9].

Regulatory relationships of Cyp1b1

  • These data are consistent with a hypothesis that TCDD stimulates the TGF-beta2 signaling pathway in the absence of the AHR to activate the Cyp1b1 gene [13].
  • These data indicate that in murine VSMCs, expression of Cyp1al and Cyp1b1 is differentially influenced by Ahr phenotype and mitogenic status, with patterns that may dictate inherent susceptibility to atherogenic stimuli [14].

Other interactions of Cyp1b1

  • Members of family CYP1 demonstrated complex, nonoverlapping embryonic patterns of expression, indicating that Cyp1a1 and Cyp1a2 may not compensate for Cyp1b1 deficiency associated with abnormal eye development [15].
  • The corresponding values for half-maximal induction response in livers of DBA/2J mice were 3.4 micrograms TCDD/kg for Cyp1b1 and 1.5 micrograms TCDD/kg for Cyp1a1 [11].
  • cDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a murine cytochrome P450 gene, Cyp1b1 [16].
  • In this report, we studied the expression patterns of Cyp1b1 in the eye of albino FVB/N mouse at different developmental stages [17].

Analytical, diagnostic and therapeutic context of Cyp1b1

  • The animals were treated i.p. with 0.001, 0.01, 0.1, 1, 10 and 50 micrograms TCDD/kg for 24 h, and Cyp1b1 and Cyp1a1 mRNA expression was analyzed by RT-PCR [11].
  • HPLC analysis of individual DMBA-DNA adducts revealed differences in the ratio of syn-DMBA-diol epoxide- to anti-DMBA-diol epoxide-derived adducts in the Ahr(-/-) and Cyp1b1(-/-) mice [18].
  • PURPOSE: To examine the embryonic expression of cytochrome P4501b1 (Cyp1b1) gene by whole mount in situ hybridization [7].
  • We isolated a cDNA fragment corresponding to the 3'untranslated region (3'UTR) of the Cyp1b1 gene by PCR and used it to make an (35)S-labelled riboprobe for in situ hybridization [17].
  • A sharp decrease in P-450-EF expression was observed both at the functional level (10- to 30-fold) (as determined by antibody inhibition studies) and at the apoprotein level (50- to > 100-fold) (as determined by Western immunoblots) [5].


  1. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. Dragin, N., Dalton, T.P., Miller, M.L., Shertzer, H.G., Nebert, D.W. J. Biol. Chem. (2006) [Pubmed]
  2. Induction of cytochromes P-450 1A1 and 1B1 by motorcycle exhaust particulate in human breast cancer MCF-7 cells. Wang, H.W., Chen, F.W., Ueng, T.H. J. Toxicol. Environ. Health Part A (2002) [Pubmed]
  3. Identification of a cytochrome P450 gene by reverse transcription--PCR using degenerate primers containing inosine. Shen, Z., Wells, R.L., Liu, J., Elkind, M.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells. Maecker, B., Sherr, D.H., Vonderheide, R.H., von Bergwelt-Baildon, M.S., Hirano, N., Anderson, K.S., Xia, Z., Butler, M.O., Wucherpfennig, K.W., O'Hara, C., Cole, G., Kwak, S.S., Ramstedt, U., Tomlinson, A.J., Chicz, R.M., Nadler, L.M., Schultze, J.L. Blood (2003) [Pubmed]
  5. Reversal of cytochrome P-4501A1 and P-450-EF expression in MCA-C3H/10T1/2 cell-derived tumors as compared to cultured cells. Christou, M., Keith, I.M., Shen, X., Schroeder, M.E., Jefcoate, C.R. Cancer Res. (1993) [Pubmed]
  6. Arsenite-induced aryl hydrocarbon receptor nuclear translocation results in additive induction of phase I genes and synergistic induction of phase II genes. Kann, S., Huang, M.Y., Estes, C., Reichard, J.F., Sartor, M.A., Xia, Y., Puga, A. Mol. Pharmacol. (2005) [Pubmed]
  7. Expression of cytochrome P4501b1 (Cyp1b1) during early murine development. Stoilov, I., Rezaie, T., Jansson, I., Schenkman, J.B., Sarfarazi, M. Mol. Vis. (2004) [Pubmed]
  8. Enhanced cytochrome P450 (Cyp1b1) expression, aryl hydrocarbon hydroxylase activity, cytotoxicity, and transformation of C3H 10T1/2 cells by dimethylbenz(a)anthracene in conditioned medium. Shen, Z., Wells, R.L., Elkind, M.M. Cancer Res. (1994) [Pubmed]
  9. Dual regulation of cytochrome P450EF expression via the aryl hydrocarbon receptor and protein stabilization in C3H/10T1/2 cells. Savas, U., Jefcoate, C.R. Mol. Pharmacol. (1994) [Pubmed]
  10. Tobacco smoke induces CYP1B1 in the aerodigestive tract. Port, J.L., Yamaguchi, K., Du, B., De Lorenzo, M., Chang, M., Heerdt, P.M., Kopelovich, L., Marcus, C.B., Altorki, N.K., Subbaramaiah, K., Dannenberg, A.J. Carcinogenesis (2004) [Pubmed]
  11. Dose-response relationship of cytochrome P4501b1 mRNA induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin in livers of C57BL/6J and DBA/2J mice. Abel, J., Li, W., Döhr, O., Vogel, C., Donat, S. Arch. Toxicol. (1996) [Pubmed]
  12. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Choudhary, D., Jansson, I., Stoilov, I., Sarfarazi, M., Schenkman, J.B. Drug Metab. Dispos. (2004) [Pubmed]
  13. Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice. Guo, J., Sartor, M., Karyala, S., Medvedovic, M., Kann, S., Puga, A., Ryan, P., Tomlinson, C.R. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  14. Constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells: role of the Ahr bHLH/PAS transcription factor. Kerzee, J.K., Ramos, K.S. Circ. Res. (2001) [Pubmed]
  15. Comparative expression profiling of 40 mouse cytochrome P450 genes in embryonic and adult tissues. Choudhary, D., Jansson, I., Schenkman, J.B., Sarfarazi, M., Stoilov, I. Arch. Biochem. Biophys. (2003) [Pubmed]
  16. cDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a murine cytochrome P450 gene, Cyp1b1. Shen, Z., Liu, J., Wells, R.L., Elkind, M.M. DNA Cell Biol. (1994) [Pubmed]
  17. Expression patterns of cytochrome P4501B1 (Cyp1b1) in FVB/N mouse eyes. Bejjani, B.A., Xu, L., Armstrong, D., Lupski, J.R., Reneker, L.W. Exp. Eye Res. (2002) [Pubmed]
  18. Role of cytochrome p4501 family members in the metabolic activation of polycyclic aromatic hydrocarbons in mouse epidermis. Kleiner, H.E., Vulimiri, S.V., Hatten, W.B., Reed, M.J., Nebert, D.W., Jefcoate, C.R., DiGiovanni, J. Chem. Res. Toxicol. (2004) [Pubmed]
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