Human Dehydroepiandrosterone Sulfotransferase

Falany, Charles N.; Comer, K A; Dooley, Thomas P.; Glatt, Hansruedi

doi:10.1111/j.1749-6632.1995.tb17372.x

Cited by 102 publications

(25 citation statements)

References 40 publications

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“…These data suggest SULT1C3 may contribute to the metabolism of steroid and phenolic compounds. Finally, SULTs 2A1 and 1E1, which are reported to metabolize steroids [29–32], both bound to and sulfonated multiple steroid and steroid-like compounds with different apparent specificities. These data show that despite the limitations of our rapid screening method, the enzymatic activity data in Table 2 reflects, to a first approximation, the expected relative substrate activities reported in the literature and reveal new activities toward pharmacologically important compounds.…”

Section: Resultsmentioning

confidence: 99%

Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases

et al. 2007

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The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism of drugs and hormones, the bioactivation of carcinogens, and the detoxification of xenobiotics. Knowledge of the structural and mechanistic basis of substrate specificity and activity is crucial for understanding steroid and hormone metabolism, drug sensitivity, pharmacogenomics, and response to environmental toxins. We have determined the crystal structures of five hSULTs for which structural information was lacking, and screened nine of the 12 hSULTs for binding and activity toward a panel of potential substrates and inhibitors, revealing unique “chemical fingerprints” for each protein. The family-wide analysis of the screening and structural data provides a comprehensive, high-level view of the determinants of substrate binding, the mechanisms of inhibition by substrates and environmental toxins, and the functions of the orphan family members SULT1C3 and SULT4A1. Evidence is provided for structural “priming” of the enzyme active site by cofactor binding, which influences the spectrum of small molecules that can bind to each enzyme. The data help explain substrate promiscuity in this family and, at the same time, reveal new similarities between hSULT family members that were previously unrecognized by sequence or structure comparison alone.

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Section: Resultsmentioning

confidence: 99%

Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases

et al. 2007

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“…SULT2A1 is responsible for sulfation of androgens. SULT2A1 is predominantly expressed in the liver, intestine, adrenal glands prostate and ovary in humans (Chen et al, 2003; Falany, 1997a,b; Falany et al, 1995; Javitt et al, 2001). SULT2A1 is expressed in the mouse liver (Alnouti & Klaassen, 2006).…”

Section: Sults In Biological Homeostasismentioning

confidence: 99%

Sulfotransferasegenes: Regulation by nuclear receptors in response to xeno/endo-biotics

Kodama¹,

Negishi²

2013

Drug Metabolism Reviews

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Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds such as steroid hormones and bile acids can also activate PXR and/or CAR. These nuclear receptors regulate genes that encode enzymes and transporters that metabolize and excrete both xenobiotics and endobiotics. Sulfotransferases (SULTs) are a group of these enzymes and sulfate xenobiotics for detoxification. In general, inactivation by sulfation constitutes the mechanism to maintain homeostasis of endobiotics. Thus, deciphering the molecular mechanism by which PXR and CAR regulate SULT genes is critical for understanding the roles of SULTs in the alterations of physiological and pathophysiological processes caused by drug treatment or environmental exposures.

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“…SULT members within this class each have preferential affinity for various substrates. For example, SULT2A1 is expressed in the liver and adrenal gland where it utilizes dehydroepiandrosterone (DHEA) as a substrate to produce and secrete the abundant circulating hormone precursor, DHEA-sulfate; SULT2A1 has been studied in PCa as a result of this function(11). SULT2B1 has two isoforms, SULT2B1a and SULT2B1b, which differ only by 15 amino acids at the N-terminus due to alternate transcriptional start sites of the same gene.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties in Prostate Cancer

Vickman

Crist

Kerian

et al. 2016

Molecular Cancer Research

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Cholesterol accumulates in prostate lesions and has been linked to prostate cancer (PCa) incidence and progression. However, how accumulated cholesterol contributes to PCa development and progression is not completely understood. Cholesterol sulfate (CS), the primary sulfonation product of cholesterol sulfotransferase (SULT2B1b), accumulates in human prostate adenocarcinoma and precancerous prostatic intraepithelial neoplasia (PIN) lesions compared to normal regions of the same tissue sample. Given the enhanced accumulation of CS in these lesions, it was hypothesized that SULT2B1b-mediated production of CS provides a growth advantage to these cells. To address this, PCa cells with RNAi-mediated knockdown (KD) of SULT2B1b were used to assess the impact on cell growth and survival. SULT2B1b is expressed and functional in a variety of prostate cells and the data demonstrate that SULT2B1b KD, in LNCaP and other androgen-responsive (VCaP and C4-2) cells, results in decreased cell growth/viability and induces cell death. SULT2B1b KD also decreases androgen receptor (AR) activity and expression at mRNA and protein levels. While AR overexpression has no impact on SULT2B1b KD-mediated cell death, addition of exogenous androgen is able to partially rescue the growth inhibition induced by SULT2B1b KD in LNCaP cells. These results suggest that SULT2B1b positively regulates the AR either through alterations in ligand availability or by interaction with critical co-regulators that influence AR activity. Implications These findings provide evidence that SULT2B1b is a novel regulator of AR activity and cell growth in prostate cancer and should be further investigated for therapeutic potential.

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Human Dehydroepiandrosterone Sulfotransferase

Cited by 102 publications

References 40 publications

Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases

Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases

Sulfotransferasegenes: Regulation by nuclear receptors in response to xeno/endo-biotics

Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties in Prostate Cancer

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