Disease relevance of Sulf1

• The Hunter syndrome gene, which causes iduronate sulfatase deficiency, is located at the X chromosome breakpoint that is distal to this new marker, thus localizing the Hunter gene distal to the fragile X locus [1].
• In conclusion, several differences were observed between human breast tumors and peritumoral tissues for many conjugating enzymes (GST-mu, GST-pi, and UDP-glucuronosyltransferase) and hydrolytic enzymes (sulfatase and beta-glucuronidase) [2].
• The protein kinase activity toward the sulfatase was considerably higher in the transplanted lung cancer than in normal lung in the presence of cAMP [3].
• All Sulf-binding clones selected following phage display contained H:Gly33, observed previously for Ars-binding Abs that use the same germline V(H) sequence [4].
• We now show that the sulfamidase gene of the MPS III A mouse carries a novel mutation (G91A) that gives an amino acid change (D31N) likely to interfere with the coordination of a divalent metal ion in the active site of this sulfatase [5].

High impact information on Sulf1

• The structural analogue of Ars p-azophenylsulfonate (Sulf) fails alone to elicit such V regions, but can do so in A/J mice previously immunized with Ars, providing a means to specifically examine B cells capable of responding secondarily to a crossreactive antigen (i.e., memory cells) [6].
• VHIdCR-expressing hybridomas were derived from the Ars-primed, Sulf-boosted original antigenic sin response of A/J mice at various times after Ars priming, and the properties of the antibodies they express and the structure of the genes encoding these antibodies were characterized [6].
• By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells [7].
• Comparison of the centrifugation behavior of PGE2 synthesis activity with that of various enzymes used as reference for the major subcellular entities has revealed that PGE2 synthesis fairly fits the density profile of sulfatase C in each case [8].
• The recently identified human sulfatase 1 enzyme (SULF1) desulfates cell surface heparan sulfate glycosaminoglycans and down-regulates cell growth signaling in HCC cells in vitro [9].

Chemical compound and disease context of Sulf1

• Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome) is a rare, autosomal recessive, lysosomal storage disease characterized by accumulation of heparan sulfate secondary to defective function of the lysosomal enzyme heparan N- sulfatase (sulfamidase) [10].

Biological context of Sulf1

• Given their possible developmental roles, we have examined Sulf gene expression during mouse embryogenesis [11].
• Such Lindane-induced vacuolation results from significant delay in autophagy degradation, in relation with a decline of the lysosomal activity of aryl sulfatase A [12].
• Increasing phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease of the activity upon overphosphorylation, using an artificial substrate [3].
• By in situ hybridization, STS messenger RNA was expressed in the embryonic mouse cortex, hindbrain, and thalamus during the last third of gestation [13].
• Potential glucuronidation/sulfation of apigenin in intact skin was assessed by measuring isolated apigenin before and after enzyme hydrolysis with glucuronidase/sulfatase [14].

Anatomical context of Sulf1

• Complementation of multiple sulfatase deficiency in somatic cell hybrids [15].
• Both sciatic nerve and embryonic brain glycolipids are hydrolyzed by glucuronidase/sulfatase treatment but are insensitive to all other glycosidases tested [16].
• Finally, we demonstrate that avian cranial surface ectoderm is patterned molecularly, with dorsolateral surface ectoderm at the levels of r2/3 and r7 expressing the sulfatase QSulf1 in quail, or the orthologue CSulf1 in chick [17].
• In addition to trimetaphosphatase activity, the lysosomes are reactive for aryl sulfatase B, thiolacetic acid esterase, and cholinesterase [18].
• We hypothesized that inhibiting STS activity in vivo followed by DHEAS injections which increase the level of sulfated steroid that cross the blood-brain barrier and then modulate neurotransmitter receptors could modify the attack behavior in mice [19].

Associations of Sulf1 with chemical compounds

• Sulf1 and Sulf2 are members of a class of recently identified genes that encode heparan sulfate 6-O-endosulfatases (Sulf genes) [11].
• The activity of the following enzymes or cofactor were determined by spectrophotometric or fluorometric assays: GST; total glutathione; UDP-glucuronosyltransferase; beta-glucuronidase; sulfotransferase; and sulfatase [2].
• Site-directed mutagenesis at H:33 indicates that Gly plays an essential structural role in HCDR1 for both Sulf- and Ars-specific Abs [4].
• High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function [20].
• Estradiol 3,17-O,O-bis-sulfamates 20 and 21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS inhibitors [21].

Other interactions of Sulf1

• These data suggest that Sulf2 may have roles in several tissues but that there is compensation by and/or redundancy with Sulf1 [11].
• Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-alpha and IFN alpha/beta [20].
• Treatment of the small intestinal contents with a preparation of beta-glucuronidase/sulfatase produced a marked increase in the amount of organic-solvent-extractable cholesterol-alpha-epoxide and other polar metabolites [22].
• The frequencies for endoplasmic reticulum and Golgi apparatus containing aryl sulfatase reaction product were highest in secretory cells, when these structures were predominant [23].

Analytical, diagnostic and therapeutic context of Sulf1

• All Fab bound Sulf, but not Ars. Site-directed mutagenesis in a variety of HCDR1 sequence contexts indicates that H:35 is critical for hapten specificity, independent of the sequence of the remainder of HCDR1 [4].
• The sulfatase gene family: cross-species PCR cloning using the MOPAC technique [24].
• By utilizing the HPLC technique in conjunction with chondroitinase ABC and AC digestion and sulfatase hydrolysis, the epimeric structures of chondroitin sulfates E and H were confirmed [25].
• Enzymatic deconjugation with bile acids sulfatase resulted in dramatically decreased urinary levels, supporting the specificity of the ELISA toward GLCA-Sul [26].
• The purified sulfatase showed a relative molecular weight of 128 kDa on HPLC gel filtration, whereas the enzyme migrated as two bands of 60 and 68 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis [27].

References