Disease relevance of ST8SIA2

• We show here that STX transcripts are present in a PSA-positive, N-CAM-positive human small cell carcinoma line (NCI-H69/F3), but are absent in a variant of this line (NCI-H69/E2) selected to be PSA-negative and N-CAM-positive [1].
• In an earlier study, we demonstrated that PSA and STX, a polysialyltransferase, were associated with tumor progression in non-small cell lung cancer (NSCLC) (F. Tanaka et al., Cancer Res., 60: 3072-3080, 2000) [2].
• Cells were transduced with a retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on NCAM [3].
• This chapter describes the use of ISH to detect ST8Sia II and ST8Sia IV mRNAs expressed in human astrocytomas using digoxigenin-labeled RNA probes [4].
• Phase I study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor [5].

Psychiatry related information on ST8SIA2

• The Sialyltransferase 8B gene (SIAT8B) is located at 15q26, a susceptibility region for both schizophrenia and bipolar disorder [6].
• We recruited 102 individuals scheduled to begin a 28-day substance use disorder (SUD) residential treatment program and randomly assigned them to receive either our standard treatment (STX) or STX plus attendance contracting and prompting (CP) [7].

High impact information on ST8SIA2

• Effects of lipophilic activators, polypeptide toxins, and, indeed, even STX and TTX are enhanced or reversed in fractions of seconds under voltage clamp by patterns of membrane potential that selectively populate the channel open state, or the slow or fast inactivated states [8].
• In summary, TTX and STX binding have been used to follow the purification of sodium channel proteins from electric organ, mammalian skeletal muscle, and brain [9].
• Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer [10].
• In contrast, the STX gene was not expressed in normal lung tissue of any case, and STX gene expression in tumor tissue was closely correlated with tumor progression [10].
• Previous studies indicate that ST8Sia IV forms more highly polysialylated N-glycans on NCAM than ST8Sia II in vitro [11].

Chemical compound and disease context of ST8SIA2

• This strategy eliminated the STX receptor-binding subunit and directed the hybrid toxins to cells expressing the HIV-1 surface glycoprotein gp120 [12].
• Sixty-three patients with acute nonlymphoid leukemia (ANLL) under cytostatic treatment were investigated in a randomized trial to determine whether oral administration of cotrimoxazole (TMP/STX) would reduce the rate of infection [13].

Biological context of ST8SIA2

• PSA-expressing Neuro2a cells (N2a-STX) were established by stable transfection of the mouse ST8Sia II gene [14].
• Moreover, the genes for PST and STX were found to reside at chromosome 5, band p21 and chromosome 15, band q26, respectively [15].
• To understand how autopolysialylation impacts ST8Sia II/STX enzymatic activity, we employed a mutagenesis approach [16].
• ST8Sia II and IV are expressed differentially in tissue-specific and cell-specific manners, and they apparently have distinct roles in development and organogenesis [17].
• Overexpression of ST8SiaII/STX wild type as well as of a mutant lacking enzymatic activity affected neuronal viability, leading to cell death [18].

Anatomical context of ST8SIA2

• The analysis by in situ hybridization of mouse adult brain, however, suggests that polysialic acid in the hippocampal formation is synthesized by both STX and PST [15].
• HeLa cells doubly transfected with the isolated STX cDNA and N-CAM cDNA supported neurite outgrowth much better than HeLa cells expressing N-CAM alone [15].
• STX is primarily expressed in embryonic tissues, but only modestly in adult heart, brain, and thymus [15].
• In addition, catalytically active, nonautopolysialylated ST8Sia II/STX does not polysialylate any endogenous COS-1 cell proteins, highlighting the protein specificity of polysialylation [16].
• Polysialic acid, a unique glycan that is developmentally regulated by two polysialyltransferases, PST and STX, in the central nervous system: from biosynthesis to function [19].

Associations of ST8SIA2 with chemical compounds

• Treatment of NCAM-Fc with Charonia lampas alpha-fucosidase, which is able to cleave alpha1,6-linked fucose, clearly reduced the polysialylation of NCAM-Fc by ST8Sia II [14].
• When fetuin and its glycopeptide and N-glycans of fetuin were used as substrates for ST8Sia II, PSA was found to be synthesized on native fetuin and its glycopeptide but not on free N-glycans [14].
• Therefore, the single enzyme, ST8Sia II, directly transferred all alpha2,8-sialic acid residues on the alpha2,3-linked sialic acids of N-glycans of specific NCAM isoforms to yield PSA-NCAM [14].
• Both ST8Sia II and IV can transfer multiple alpha 2,8-linked sialic acid residues to an acceptor N-glycan containing a NeuNAc alpha 2-->3 (or 6) Gal beta 1-->4GlcNAc beta 1-->R structure without participation of other enzymes [17].
• The members of the ST8Sia gene family, including ST8Sia II and ST8Sia IV are unique in having three cysteines in sialylmotif L, one cysteine in sialylmotif S, and one cysteine at the COOH terminus [20].

Physical interactions of ST8SIA2

• We first examined whether PST and STX differ in the requirement of sialic acid and core structures of N-glycans attached to NCAM [21].

Other interactions of ST8SIA2

• These discoveries prompted us to determine if ST8Sia IV and ST8Sia II share the property of ST8Sia III in utilizing low molecular weight oligosaccharides as acceptors [22].
• However, whether the autopolysialylation of ST8Sia II/STX is required for its ability to polysialylate NCAM is unknown [16].
• Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia [23].

Analytical, diagnostic and therapeutic context of ST8SIA2

• Northern blot analysis, using this cDNA and PST cDNA previously isolated by us, demonstrated that PST and STX are expressed in different fetal and adult tissues [15].
• Analysis of these high molecular mass forms by glycosidase digestion and serial immunoprecipitation/immunoblot experiments demonstrated that PST and STX are autopolysialylated in vivo [24].
• Sequence analysis of the 3'-untranslated region of ST8SiaII/STX cDNA indicated putative regulatory motifs [18].
• Polysialyltransferase expression levels analyzed by real-time RT-PCR indicated that ST8SiaII/STX mRNA is markedly down-regulated in vivo, decreasing abruptly at about the first week of postnatal development [18].
• The number of tetrodotoxin (TTX)-sensitive Na-channels was determined by measurements of the amount of [3H]saxitoxin (STX) bound to the cultures, and electrical properties were recorded with intracellular microelectrodes [25].

References