UGT1A1/7 Variants. Drug Metab. Dispos. 42, 229–238. doi:10.1124/dmd.113.
054833
Ishii, Y., Takeda, S., and Yamada, H. (2010). Modulation of UDPGlucuronosyltransferase Activity by Protein-Protein Association. Drug
Metab. Rev. 42, 145–158. doi:10.3109/03602530903208579
Jarvis, D. L. (2003). Developing Baculovirus-Insect Cell Expression Systems for
Humanized Recombinant Glycoprotein Production. Virology 310, 1–7. doi:10.
1016/s0042-6822(03)00120-x
Khan, K. H. (2013). Gene Expression in Mammalian Cells and its Applications.
Adv. Pharm. Bull. 3, 257–263. doi:10.5681/apb.2013.042
Kruh, J. (1982). Effects of Sodium Butyrate, a New Pharmacological Agent, on Cells
in Culture. Mol. Cel. Biochem. 42, 65–82. doi:10.1007/BF00222695
Kumondai, M., Hishinuma, E., Gutiérrez Rico, E. M., Ito, A., Nakanishi, Y.,
Saigusa, D., et al. (2020). Heterologous Expression of High-Activity
Cytochrome P450 in Mammalian Cells. Sci. Rep. 10, 14193. doi:10.1038/
s41598-020-71035-5
Kusano, K., Waterman, M. R., Sakaguchi, M., Omura, T., and Kagawa, N. (1999).
Protein Synthesis Inhibitors and Ethanol Selectively Enhance Heterologous
Expression of P450s and Related Proteins in Escherichia C. Arch. Biochem.
Biophys. 367, 129–136. doi:10.1006/abbi.1999.1248
Luckow, V. A. (1993). Baculovirus Systems for the Expression of Human Gene
Products. Curr. Opin. Biotechnol. 4, 564–572. doi:10.1016/0958-1669(93)
90078-b
Mackenzie, P. I. (1986). Rat Liver UDP-Glucuronosyltransferase. cDNA Sequence
and Expression of a Form Glucuronidating 3-Hydroxyandrogens. J. Biol. Chem.
261, 14112–14117. doi:10.1016/s0021-9258(18)66989-3
Mackenzie, P. I. (1990). The Effect of N-Linked Glycosylation on the Substrate
Preferences of UDP Glucuronosyltransferases. Biochem. Biophys. Res.
Commun. 166, 1293–1299. doi:10.1016/0006-291x(90)91006-e
Makkonen, K. E., Airenne, K., and Ylä-Herttulala, S. (2015). Baculovirus-Mediated
Gene Delivery and RNAi Applications. Viruses 7, 2099–2125. doi:10.3390/
v7042099
Marchal, I., Jarvis, D. L., Cacan, R., and Verbert, A. (2001). Glycoproteins from
Insect Cells: Sialylated or Not? Biol. Chem. 382, 151–159. doi:10.1515/BC.
2001.023
Miyauchi, Y., Kurita, A., Yamashita, R., Takamatsu, T., Ikushiro, S., Mackenzie, P.
I., et al. (2020a). Hetero-oligomer Formation of Mouse UDPGlucuronosyltransferase (UGT) 2b1 and 1a1 Results in the Gain of
Glucuronidation Activity towards Morphine, an Activity Which Is Absent
in Homo-Oligomers of Either UGT. Biochem. Biophys. Res. Commun. 525,
348–353. doi:10.1016/j.bbrc.2020.02.075
Miyauchi, Y., Kurohara, K., Kimura, A., Esaki, M., Fujimoto, K., Hirota, Y., et al.
(2020b). The Carboxyl-Terminal Di-lysine Motif Is Essential for Catalytic
Activity of UDP-Glucuronosyltransferase 1A9. Drug Metab. Pharmacokinet.
35, 466–474. doi:10.1016/j.dmpk.2020.07.006
Miyauchi, Y., Nagata, K., Yamazoe, Y., Mackenzie, P. I., Yamada, H., and Ishii, Y.
(2015). Suppression of Cytochrome P450 3A4 Function by UDPGlucuronosyltransferase 2B7 through a Protein-Protein Interaction:
Cooperative Roles of the Cytosolic Carboxyl-Terminal Domain and the
Luminal Anchoring Region. Mol. Pharmacol. 88, 800–812. doi:10.1124/mol.
115.098582
Miyauchi, Y., Takechi, S., and Ishii, Y. (2021). Functional Interaction between
Cytochrome P450 and UDP-Glucuronosyltransferase on the Endoplasmic
Reticulum Membrane: One of post-translational Factors Which Possibly
Contributes to Their Inter-Individual Differences. Biol. Pharm. Bull. 44,
1635–1644. doi:10.1248/bpb.b21-00286
Miyauchi, Y., Yamada, H., and Ishii, Y. (2019). Advantage of a Co-Expression
System for Estimating Physiological Effects of Functional Interaction between
Cytochrome P450 3A4 and Uridine 5’-Diphospho-Glucuronosyltransferase
2B7. BPB Rep. 2, 61–66. doi:10.1248/bpbreports.2.5_61
Morales-Perez, C. L., Noviello, C. M., and Hibbs, R. E. (2016). Manipulation of
Subunit Stoichiometry in Heteromeric Membrane Proteins. Structure 24,
797–805. doi:10.1016/j.str.2016.03.004
Nagaoka, K., Hanioka, N., Ikushiro, S., Yamano, S., and Narimatsu, S. (2012). The
Effects of N-Glycosylation on the Glucuronidation of Zidovudine and
Morphine by UGT2B7 Expressed in HEK293 Cells. Drug Metab.
Pharmacokinet. 27, 388–397. doi:10.2133/dmpk.dmpk-11-rg-135
Aoyama, K., Yoshinari, K., Kim, H. J., Nagata, K., and Yamazoe, Y. (2009).
Simultaneous Expression of Plural Forms of Human Cytochrome P450 at
Desired Ratios in HepG2 Cells: Adenovirus-Mediated Tool for Cytochrome
P450 Reconstitution. Drug Metab. Pharmacokinet. 24, 209–217. doi:10.2133/
dmpk.24.209
Asseffa, A., Smith, S. J., Nagata, K., Gillette, J., Gelboin, H. V., and Gonzalez, F. J.
(1989). Novel Exogenous Heme-Dependent Expression of Mammalian
Cytochrome P450 Using Baculovirus. Arch. Biochem. Biophys. 274, 481–490.
doi:10.1016/0003-9861(89)90461-x
Backes, W. L., and Kelley, R. W. (2003). Organization of Multiple Cytochrome
P450s with NADPH-Cytochrome P450 Reductase in Membranes. Pharmacol.
Ther. 98, 221–233. doi:10.1016/s0163-7258(03)00031-7
Barbier, O., Girard, C., Breton, R., Bélanger, A., and Hum, D. W. (2000).
N-Glycosylation and Residue 96 Are Involved in the Functional Properties
of UDP-Glucuronosyltransferase Enzymes. Biochemistry 39, 11540–11552.
doi:10.1021/bi000779p
Boyce, F. M., and Bucher, N. L. (1996). Baculovirus-Mediated Gene Transfer into
Mammalian Cells. Proc. Natl. Acad. Sci. U. S. A. 93, 2348–2352. doi:10.1073/
pnas.93.6.2348
Clark, B. J., and Waterman, M. R. (1991). Heterologous Expression of Mammalian
P450 in COS Cells. Methods Enzymol. 206, 100–108. doi:10.1016/00766879(91)06081-d
Condreay, J. P., Witherspoon, S. M., Clay, W. C., and Kost, T. A. (1999). Transient
and Stable Gene Expression in Mammalian Cells Transduced with a
Recombinant Baculovirus Vector. Proc. Natl. Acad. Sci. U. S. A. 96,
127–132. doi:10.1073/pnas.96.1.127
Court, M. H. (2010). Interindividual Variability in Hepatic Drug Glucuronidation:
Studies into the Role of Age, Sex, Enzyme Inducers, and Genetic Polymorphism
Using the Human Liver Bank as a Model System. Drug Metab. Rev. 42, 209–224.
doi:10.3109/03602530903209288
Crespi, C. L., and Miller, V. P. (1999). The Use of Heterologously Expressed Drug
Metabolizing Enzymes-State of the Art and Prospects for the Future.
Pharmacol. Ther. 84, 121–131. doi:10.1016/s0163-7258(99)00028-5
Duisit, G., Saleun, S., Douthe, S., Barsoum, J., Chadeuf, G., and Moullier, P. (1999).
Baculovirus Vector Requires Electrostatic Interactions Including Heparan
Sulfate for Efficient Gene Transfer in Mammalian Cells. J. Gene Med. 1,
93–102.
doi:10.1002/(SICI)1521-2254(199903/04)1:2<93:AID-JGM19>3.0.
CO;2-1
Evans, W. E., and Relling, M. V. (1999). Pharmacogenomics: Translating
Functional Genomics into Rational Therapeutics. Science 286, 487–491.
doi:10.1126/science.286.5439.487
Finel, M., and Kurkela, M. (2008). The UDP-Glucuronosyltransferases as
Oligomeric Enzymes. Curr. Drug Metab. 9, 70–76. doi:10.2174/
138920008783331158
Gluzman, Y. (1981). SV40-Transformed Simian Cells Support the Replication of
Early SV40 Mutants. Cell 23, 175–182. doi:10.1016/0092-8674(81)90282-8
Gorman, C. M., Howard, B. H., and Reeves, R. (1983). Expression of Recombinant
Plasmids in Mammalian Cells Is Enhanced by Sodium Butyrate. Nucleic Acids
Res. 11, 7631–7648. doi:10.1093/nar/11.21.7631
Guengerich, F. P. (2006). Cytochrome P450s and Other Enzymes in Drug
Metabolism and Toxicity. AAPS J. 8, E101–E111. doi:10.1208/aapsj080112
Guengerich, F. P., Parikh, A., Johnson, E. F., Richardson, T. H., Von Wachenfeldt,
C., Cosme, J., et al. (1997). Heterologous Expression of Human DrugMetabolizing Enzymes. Drug Metab. Dispos. 25, 1234–1241.
Hofmann, C., Sandig, V., Jennings, G., Rudolph, M., Schlag, P., and Strauss, M.
(1995). Efficient Gene Transfer into Human Hepatocytes by Baculovirus
Vectors. Proc. Natl. Acad. Sci. U. S. A. 92, 10099–10103. doi:10.1073/pnas.
92.22.10099
Hu, Y. C. (2005). Baculovirus as a Highly Efficient Expression Vector in Insect and
Mammalian Cells. Acta Pharmacol. Sin. 26, 405–416. doi:10.1111/j.1745-7254.
2005.00078.x
Ishii, Y., Koba, H., Kinoshita, K., Oizaki, T., Iwamoto, Y., Takeda, S., et al. (2014).
Alteration of the Function of the UDP-Glucuronosyltransferase 1A Subfamily
by Cytochrome P450 3A4: Different Susceptibility for UGT Isoforms and
Frontiers in Pharmacology | www.frontiersin.org
February 2022 | Volume 13 | Article 832931
Miyauchi et al.
Bac-Mam System for Drug-Metabolizing Enzymes
To-Phenotype Studies. Pharmacogenomics J. 2, 48–56. doi:10.1038/sj.tpj.
6500089
Volkman, L. E., and Goldsmith, P. A. (1983). In Vitro Survey of Autographa Californica
Nuclear Polyhedrosis Virus Interaction with Nontarget Vertebrate Host Cells. Appl.
Environ. Microbiol. 45, 1085–1093. doi:10.1128/AEM.45.3.1085-1093.1983
Zanger, U. M., and Schwab, M. (2013). Cytochrome P450 Enzymes in Drug Metabolism:
Regulation of Gene Expression, Enzyme Activities, and Impact of Genetic Variation.
Pharmacol. Ther. 138, 103–141. doi:10.1016/j.pharmthera.2012.12.007
Zhang, H., Patana, A. S., Mackenzie, P. I., Ikushiro, S., Goldman, A., and Finel, M.
(2012). Human UDP-Glucuronosyltransferase Expression in Insect Cells: Ratio
of Active to Inactive Recombinant Proteins and the Effects of a C-Terminal HisTag on Glucuronidation Kinetics. Drug Metab. Dispos. 40, 1935–1944. doi:10.
1124/dmd.112.046086
Nakajima, M., Koga, T., Sakai, H., Yamanaka, H., Fujiwara, R., and Yokoi, T.
(2010). N-Glycosylation Plays a Role in Protein Folding of Human UGT1A9.
Biochem. Pharmacol. 79, 1165–1172. doi:10.1016/j.bcp.2009.11.020
Nakamura, T., Yamaguchi, N., Miyauchi, Y., Takeda, T., Yamazoe, Y., Nagata, K.,
et al. (2016). Introduction of an N-Glycosylation Site into UDPGlucuronosyltransferase 2B3 Alters its Sensitivity to Cytochrome P450 3A1Dependent Modulation. Front. Pharmacol. 7, 427. doi:10.3389/fphar.2016.
00427
Oda, S., Nakajima, M., Hatakeyama, M., Fukami, T., and Yokoi, T. (2012).
Preparation of a Specific Monoclonal Antibody against Human UDPGlucuronosyltransferase (UGT) 1A9 and Evaluation of UGT1A9 Protein
Levels in Human Tissues. Drug Metab. Dispos. 40, 1620–1627. doi:10.1124/
dmd.112.045625
Omura, T., and Sato, R. (1964). The carbon monoxide-binding pigment of liver
microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239,
2370–2378.
Ramos, L., Kopec, L. A., Sweitzer, S. M., Fornwald, J. A., Zhao, H., Mcallister, P.,
et al. (2002). Rapid Expression of Recombinant Proteins in Modified CHO Cells
Using the Baculovirus System. Cytotechnology 38, 37–41. doi:10.1023/A:
1021189628274
Shin, H., Lee, Y. S., and Lee, Y. C. (2012). Sodium Butyrate-Induced DAPKMediated Apoptosis in Human Gastric Cancer Cells. Oncol. Rep. 27,
1111–1115. doi:10.3892/or.2011.1585
Sugatani, J. (2013). Function, Genetic Polymorphism, and Transcriptional
Regulation of Human UDP-Glucuronosyltransferase (UGT) 1A1. Drug
Metab. Pharmacokinet. 28, 83–92. doi:10.2133/dmpk.dmpk-12-rv-096
Tani, H., Nishijima, M., Ushijima, H., Miyamura, T., and Matsuura, Y. (2001).
Characterization of Cell-Surface Determinants Important for Baculovirus
Infection. Virology 279, 343–353. doi:10.1006/viro.2000.0699
Thomae, B. A., Eckloff, B. W., Freimuth, R. R., Wieben, E. D., and Weinshilboum,
R. M. (2002). Human Sulfotransferase SULT2A1 Pharmacogenetics: Genotype-
Frontiers in Pharmacology | www.frontiersin.org
Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Publisher’s Note: All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated organizations, or those of
the publisher, the editors and the reviewers. Any product that may be evaluated in
this article, or claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
Copyright © 2022 Miyauchi, Kimura, Sawai, Fujimoto, Hirota, Tanaka, Takechi,
Mackenzie and Ishii. This is an open-access article distributed under the terms of the
Creative Commons Attribution License (CC BY). The use, distribution or
reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal is
cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
10
February 2022 | Volume 13 | Article 832931
...