Disease relevance of ST8SIA4

• In comparison, polysialyltransferase mRNA levels are not regulated in neuroblastoma cells during their proliferation [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].
• Pancreatitis risk was increased 14-fold by having the N34S PST1 mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both [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].
• Polysialic acid engineering: synthesis of polysialylated neoglycosphingolipids by using the polysialyltransferase from neuroinvasive Escherichia coli K1 [5].

Psychiatry related information on ST8SIA4

• Phenserine (PS) was designed as a selective acetylcholinesterase (AChE) inhibitor, with a tartrate form (PST) for oral administration in mild to moderate Alzheimer's disease (AD) [6].

High impact information on ST8SIA4

• In contrast to the polysialylation of NCAM, where terminal sialylation in either the alpha2,3 or alpha2,6 position is required, the autopolysialylation could be started in the asialo-PST-1 isolated from CHO cells of the Lec2 complementation group [7].
• It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA [8].
• The deduced amino acid sequence indicates that the polysialyltransferase shares a common sequence motif with other sialyltransferases cloned so far [9].
• Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer [10].
• Cocultures of CG neurons with myotubes were used to provide direct evidence that neuron-muscle interaction can cause a specific downregulation of both neuronal PSA and polysialyltransferase activity [11].

Chemical compound and disease context of ST8SIA4

• The objective of the present study was to assess the potential predictive value of supine morning plasma aldosterone concentration, a component of the postural stimulation test (PST), in distinguishing aldosterone-producing adenoma (APA) from idiopathic adrenal hyperplasia (IAH) in a series of 61 patients with confirmed primary aldosteronism (PAL) [12].

Biological context of ST8SIA4

• The cloning and characterization of two polysialyltransferases, termed ST8SiaII (STX) and ST8SiaIV (PST), opened up new perspectives in the search for factors that control this unique cell surface glycosylation [13].
• We first determined the catalytic domain of ST8Sia IV by deletion mutants [14].
• To understand the role of autopolysialylation in PST enzymatic activity, we employed a mutagenesis approach [15].
• METHODS: We performed an association study of single nucleotide polymorphisms (SNPs) within SIAT8B and SIAT8D, using 188 schizophrenics and 156 age and gender matched controls [16].
• These data are consistent with a model in which Pst1p-Clr6p temporally associate with centromeres to carry out the initial deacetylation necessary for subsequent steps in heterochromatin formation [17].

Anatomical context of ST8SIA4

• Differential regulation of polysialyltransferase expression during hippocampus development: Implications for neuronal survival [1].
• Interestingly, the overexpressed polysialyltransferase accumulates not only in the perinuclear region but also in the plasma membrane [1].
• Indirect immunofluorescence microscopy and immunoprecipitation analyses demonstrated that autopolysialylated PST and STX are localized in the Golgi, on the cell surface, and in the extracellular space [18].
• Notably, catalytically active, non-autopolysialylated PST does not polysialylate any endogenous COS-1 cell proteins, highlighting the protein specificity of polysialylation [15].
• However, N-butanoylmannosamine and N-pentanoylmannosamine are effective inhibitors of polysialic acid (PSA) synthesis in stably transfected HeLa cells expressing NCAM and the polysialyltransferase STX [19].

Associations of ST8SIA4 with chemical compounds

• 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].
• PST and STX were found to add polysialic acid on NCAM.Fc molecules sialylated by alpha-2,3- or alpha-2,6-linkage in vitro, but not on NCAM.Fc lacking either sialic acid [21].
• Molecular dissection of the ST8Sia IV polysialyltransferase. Distinct domains are required for neural cell adhesion molecule recognition and polysialylation [14].
• Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids [22].
• In accord with this hypothesis, the polyanion heparin was shown to inhibit recombinant human ST8Sia II and ST8Sia IV at 10 muM [23].

Physical interactions of ST8SIA4

• Furthermore, ST8Sia IV was able to add polysialic acid to oligosialylated oligosaccharides and unpolysialylated antennas in N-glycans attached to NCAM, even when polysialic acid was attached to at least one of the other antennas [24].

Enzymatic interactions of ST8SIA4

• We found that BACE1 cleaved polysialyltransferase ST8Sia IV (PST) in vitro [25].

Other interactions of ST8SIA4

• The polysialyltransferase ST8Sia II/STX: posttranslational processing and role of autopolysialylation in the polysialylation of neural cell adhesion molecule [26].
• To obtain insight into the structure/function of ST8Sia IV, we expressed human ST8Sia IV in insect cells, Trichoplusia ni, and found that the enzyme produced in the insect cells catalyzes NCAM polysialylation, although it cannot polysialylate itself ("autopolysialylation") [20].
• However, chimeric enzymes that contain only the carboxyl-terminal segment of ST8Sia IV and the amino-terminal segment of ST8Sia III showed very weak activity toward NCAM, even though they had strong activity in polysialylating themselves [14].
• The occurrence of novel 9-O-sulfated N-glycolylneuraminic acid-capped alpha2-->5-Oglycolyl-linked oligo/polyNeu5Gc chains in sea urchin egg cell surface glycoprotein. Identification of a new chain termination signal for polysialyltransferase [27].
• All blood leukocytes expressed ST8Sia IV, implicated in polysialic acid synthesis, and NK cells variably expressed high levels of ST8Sia V mRNA required for GT3 expression [28].

Analytical, diagnostic and therapeutic context of ST8SIA4

• 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 [1].
• This review focuses on the molecular cloning of human polysialyltransferase, designated PST [29].
• Analysis of these high molecular mass forms by glycosidase digestion and serial immunoprecipitation/immunoblot experiments demonstrated that PST and STX are autopolysialylated in vivo [18].
• Reverse transcription-PCR showed simultaneous expression of the two enzymes, and in situ hybridization demonstrated that the polysialyltransferase mRNA expression parallels immunoreactivity with the PSA-specific monoclonal antibody 735 [30].
• Site-directed mutagenesis showed that Ile(275), Lys(276) and Arg(277) in the C-terminus of PSTD in ST8Sia IV, which is contiguous with the N-terminus of sialylmotif-S, were essential for polysialylation [23].

References