Disease relevance of CHST11

• Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32) [1].
• We showed previously that purified C4ST-1 from the culture medium of rat chondrosarcoma cells was a glycoprotein containing approx. 35% N-linked oligosaccharides [2].
• These results suggest that C4ST-1 regulates the expression of the E disaccharide unit and the length of CS chains, the features that facilitate infection of cells by HSV-1 [3].
• Chondroitin 4-o-sulfotransferase-1 regulates e disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity [3].
• Since the C4S-adherent IRBCs that enter the fetal blood vessels cannot adhere to the cord endothelial surface and parasites cannot efficiently grow due to fetal hemoglobin toxicity and protection by maternal antibodies, transplacental infection may be quickly cleared without clinical episodes [4].

High impact information on CHST11

• Here we studied the detailed C4S structural requirements by assessing the ability of chemically modified C4S to inhibit IRBC binding to the placental chondroitin sulfate proteoglycan [5].
• A dodecasaccharide motif of the low-sulfated chondroitin 4-sulfate (C4S) mediate the binding of Plasmodium falciparum-infected red blood cells (IRBCs) in human placenta [5].
• Conjugation of biotin to the C4S dodecasaccharide photoaffinity probe afforded a strategy for the isolation of the labeled protein by avidin affinity precipitation, facilitating efforts to identify the C4S-adherent IRBC protein(s) [5].
• RT-PCR revealed that sog9 cells had a defect in the expression of C4ST-1 in addition to EXT1 [3].
• Transfer of C4ST-1 cDNA into sog9 cells (sog9-C4ST-1) restored 4-O-sulfation and amount of CS, verifying that sog9 cells had a specific defect in C4ST-1 [3].

Chemical compound and disease context of CHST11

• We showed previously that C4ST-1 purified from rat chondrosarcoma and recombinant C4ST-1 both transfer sulphate efficiently to position 4 of the GalNAc residues of DSDS (desulphated dermatan sulphate) [6].
• Furthermore, the expression of C4ST-1 rendered sog9 cells significantly more susceptible to HSV-1 infection, suggesting that CS modified by C4ST-1 is sufficient for the binding and infectivity of HSV-1 [3].
• At 30 days after TAC injection, HA and C4S were not detected by electrophoresis in keloid implants; only dermatan sulfate appeared to be present [7].
• In contrast, the injections of TAC at a level that caused temporary body weight loss in the mice resulted in significant decreases in both hyaluronic acid (HA) and C4S in the keloid implants [7].
• To test whether chondroitin sulfate (CS) isomers in synovial fluid are related to the radiographic severity of osteoarthritis (OA) and the age and sex, we investigated the concentrations of chondroitin 6-sulfate (C6S) and chondroitin 4-sulfate (C4S) in patients with OA of the knee joint and age-matched healthy controls [8].

Biological context of CHST11

• Both fusion species contained open reading frames making possible the translation of two truncated forms of CHST11 protein [1].
• The protein has an amino acid sequence homology of 96% with mouse C4ST [9].
• The cDNA was isolated from a human fetal brain cDNA library by hybridization with a DNA probe prepared from rat poly(A)(+) RNA used for the cloning of mouse C4ST cDNA [9].
• The C4ST gene was localized to chromosome 12q23.2-q23.3 by fluorescence in situ hybridization [9].
• These results in conjunction with studies on peptide variants (i.e., C4S, C6S, and Y7F) demonstrate unequivocally the key role of biological dithiols in both the dealkylation and binding of organotin compounds [10].

Anatomical context of CHST11

• Northern analysis demonstrated that the transcript for C4ST-1 is predominantly expressed in peripheral leukocytes and hematopoietic tissues while the C4ST-2 transcript is more widely expressed in various tissues [11].
• OBJECTIVE: To examine how age and sex influence chondroitin sulfates (CS) in normal synovial fluid, we measured the concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and hyaluronic acid (HA) in healthy subjects of different ages [12].
• On the other hand, TGF-beta1 increases total GAG synthesis in immature, but not mature, cartilage (stimulates CS but not non-CS), age-independently decreases C6S:C4S (more C4S), and increases chondrocyte UDPGD activity in a manner inversely correlated with age [13].
• These data suggest that C4S may contribute to protect LDL against oxidation in arterial intima [14].
• When fibroblasts were treated with two different doses of HYA or C4S a protective effect, following oxidative stress induction, was shown [15].

Associations of CHST11 with chemical compounds

• The biological consequence of t(12;14)(q23;q32) in this case presumably is a disturbance of the cellular distribution of CHST11 leading to deregulation of a chondroitin-sulfate-dependent pathway specific to the hematopoietic lineage [1].
• Chondroitin 4-sulfotransferase (C4ST) catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of the N-acetylgalactosamine residues of chondroitin [9].
• Moreover, analysis of (35)S-labeled dermatan sulfate formed by C4ST-1 indicate that sulfation preferentially took place in GlcA-->GalNAc unit than in IdoA-->GalNAc unit, suggesting that 4-O-sulfation at N-acetylgalactosamine may precede epimerization of glucuronic acid to iduronic acid during dermatan sulfate biosynthesis [11].
• The predicted sequence of the protein contains all of the known amino acid sequence and four potential sites for N-glycosylation, which corresponds to the observation that the purified C4ST is an N-linked glycoprotein [16].
• Levels of chondroitin 6-sulfate (C6S), C4S, and hyaluronic acid were measured with high-performance liquid chromatography [17].

Other interactions of CHST11

• On the other hand, chondroitin 4-O sulfotransferase activity increased 2-fold upon TGF-beta1 treatment and 3-fold upon treatment with the growth factor combination [18].
• Three more carboxyl-terminal regions of unknown function also show a high degree of identity with HNK-1 ST, C4ST-1, and C4ST-2 [19].
• These results indicate C4ST-1 and C4ST-2 play complementary roles in chondroitin and dermatan sulfate synthesis in different tissues [11].
• These newly cloned enzymes, termed GalNAc4ST-1 and GalNAc4ST-2, belong to the HNK-1ST gene family having 40--42% identity with C4ST-1 [20].

Analytical, diagnostic and therapeutic context of CHST11

• Northern Blot analysis of tumor RNA using CHST11-specific probes showed expression of two CHST11 forms of abnormal size [1].
• Molecular cloning, expression, and chromosomal mapping of human chondroitin 4-sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase [9].
• After intravenous or intraperitoneal injections, C4S analog and the nonmutated chicken and ovine leptins all lowered the food intake of starved 9-day-old broiler or 5-wk-old layer male chickens by 11-34% [21].
• Gingival tissue C4S levels in the overgrowth group were significantly higher than the healthy control group at baseline (p=0.000) [22].
• Clinical data were recorded, and the levels of the GAG hyaluronan (HA) and chondroitin-4-sulphate (C4S) were assessed using cellulose acetate electrophoresis and densitometric scanning of Alcian blue-stained strips against known GAG standards [23].

References