Cytosolic STs sulfate xenochemicals for detoxification and secretion and also sulfate biological signal molecules such as steroid hormones and bioamines for inactivation and/or storage. Certain sulfated products become carcinogenic. Golgi-membrane STs display high specificity to sulfate distinct sites of polysaccharides. Various glycosyltransferases synthesize polysaccharides and provide STs with substrates. Our research objectives are to eluciadte structure and function of these enzymes. For this, we have used bacterial expression system to produce a large amount of recombinant proteins, have crystallized them, and have solved their 3-dimensional structures. Also Isothermal titration carlimetry is used to investigate various molecular interactactions in solution.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES071005-09
Application #
7593958
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2007
Total Cost
$388,077
Indirect Cost
City
State
Country
United States
Zip Code
Hashiguchi, Takuyu; Shindo, Sawako; Chen, Shih-Heng et al. (2018) Sulfotransferase 4A1 Increases Its Expression in Mouse Neurons as They Mature. Drug Metab Dispos 46:860-864
Negishi, Masahiko (2017) Phenobarbital Meets Phosphorylation of Nuclear Receptors. Drug Metab Dispos 45:532-539
Hori, Takeshi; Moore, Rick; Negishi, Masahiko (2016) p38 MAP Kinase Links CAR Activation and Inactivation in the Nucleus via Phosphorylation at Threonine 38. Drug Metab Dispos 44:871-6
Li, Linhao; Li, Haishan; Garzel, Brandy et al. (2015) SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liver. Mol Pharmacol 87:674-82
Gotoh, Saki; Negishi, Masahiko (2015) Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis. Sci Rep 5:14076
Sueyoshi, Tatsuya; Li, Linhao; Wang, Hongbing et al. (2014) Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes. Toxicol Sci 137:292-302
Saito, Kosuke; Moore, Rick; Negishi, Masahiko (2013) Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia. Toxicol Sci 132:151-61
Shindo, Sawako; Sakuma, Tsutomu; Negishi, Masahiko et al. (2012) Phosphorylation of serine 212 confers novel activity to human estrogen receptor ?. Steroids 77:448-53
Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko (2011) Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver. Lab Invest 91:1624-33
Yamamoto, Yukio; Moore, Rick; Flavell, Richard A et al. (2010) Nuclear receptor CAR represses TNFalpha-induced cell death by interacting with the anti-apoptotic GADD45B. PLoS One 5:e10121

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