Disease relevance of St8sia4

• Transfection with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene revealed that the promoter activity of the -107/+145 region was correlated with the gene expression of mST8Sia IV/PST in embryonal carcinoma P19 and neuroblastoma F11 cells [1].
• Proviruses acquired during infection of BALB/c mice foster-nursed by virus-producing C3H females can be distinguished from the MMTV proviruses endogenous to uninfected BALB/c mice by the nature of the fragments generated with Pst I and Bam HI [2].
• All but 1 of the late mammary adenocarcinomas had MuMTV antigens detected by peroxidase antiperoxidase staining, and all contained the 0.92- and 4.0-kb exogenous virus Pst I fragments [3].
• Double-stranded cDNA synthesized from this mRNA was inserted into the Pst I site of plasmid pBR322 by using oligo(dG . dC)-tailing and was propagated in Escherichia coli [4].
• The latter include outer membrane peptides (Yops) known to undergo Pst plasmid-mediated post-translational degradation in Yersinia pestis but not in enteropathogenic yersiniae lacking this plasmid [5].

Psychiatry related information on St8sia4

• We report that ST8SiaIV knockout mice were impaired in spatial as well as reversal learning in the water maze [6].

High impact information on St8sia4

• All early tumors were MuMTV antigen-positive mammary adenocarcinomas that contained the 0.92- and 4.0-kilo base (kb) exogenous C3H MuMTV-specific Pst I restriction endonuclease fragments [3].
• To investigate the molecular functions of the Eya gene products, we have analyzed whether the highly divergent PST (proline-serine-threonine)-rich N-terminal regions of Eya1-3 function as transactivation domains [7].
• The cDNA insert of one recombinant plasmid (clone P-16 alpha-1) was 1.75 kilobases in size and contained one or more internal restriction sites for HindIII, BamHI, Bgl I, Pst I, Alu I, HinpI, and Rsa I [8].
• Contrary to NCAM mutant mice, LTP in ST8SiaIV mutants was undisturbed at mossy fiber-CA3 synapses, which do not express PSA in wild-type mice [9].
• Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV [10].

Chemical compound and disease context of St8sia4

• Double-stranded DNA complementary to total poly(A)+RNA derived from a mouse pituitary thyrotropic tumor was prepared enzymatically, inserted into the Pst I site of the plasmid pBR322 by using poly(dC).poly(dG) homopolymeric extensions, and cloned in Escherichia coli chi 1776 [11].
• Double-stranded cDNA was synthesized from sucrose gradient-purified poly(A)+ mRNA from a mouse thyrotropic tumor, inserted into the Pst I site of plasmid pBR322 by using poly(dC) . poly(dG) homopolymeric extensions, and cloned in Escherichia coli RRI [12].
• A retroviral vector containing a 4.4-kb Pst I human beta S-globin gene and a neomycin resistance gene was used to infect NIH-3T3 and mouse erythroleukemia cells (MELC) [13].

Biological context of St8sia4

• The mST8Sia IV/PST gene was found to comprise over 60 kilobases and to be composed of five exons [1].
• Similar to the wild-type genotype, long polySia chains (>50 residues) were detected in all genotypes expressing at least one functional polysialyltransferase allele [10].
• Mobility shift assaying also revealed that Sp1 and NF-Y in a nuclear extract of P19 cells bind to the promoter region of the mST8Sia IV/PST gene [1].
• These results, taken together, strongly suggest that PST and STX are expressed distinctly in tissue-specific and cell-specific manners and that they apparently have distinct roles in development and organogenesis [14].
• Deletion of the region from -60 to -40, which contains parts of both the Sp1 and NF-Y binding sites, completely abolished the promoter activity, suggesting that both Sp1 and NF-Y are synergetically involved in transcription regulation of the mST8Sia IV/PST gene in P19 and F11 cells [1].

Anatomical context of St8sia4

• PST, on the other hand, is continuously expressed in adult heart, brain, thymus, spleen, small and large intestines, and peripheral blood leukocytes [14].
• Thus, although decreased in activity in PSA-negative cell lines, the basal promoter is not sufficient for the strong cell-type and tissue specific regulation of the ST8SiaIV gene, suggesting regulatory elements in the more upstream 5'-region [15].
• Finally, evidence that the two polysialyltransferases, PST and STX, apparently have distinct roles in the development of neural cells is provided by using a neurite outgrowth assay [16].
• In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus [17].
• In this study, we examined the expression of PSA as well as 2 polysialyltransferases, PST and STX, in various tumor cell lines [18].

Associations of St8sia4 with chemical compounds

• AcDNA encoding a new alpha2,8-sialyltransferase (ST8Sia IV), which exhibits activity toward the alpha,2,3-linked sialic acids of N-linked oligosaccharides, was cloned from a mouse lung cDNA library by means of the PCR-based approach [19].
• Our results also show that PST-1 can act on core structures with the terminal sialic acid connected to galactose via an alpha2,3 or alpha2,6 linkage [20].
• Modulation of peroxisome proliferator-activated receptor delta activity affects neural cell adhesion molecule and polysialyltransferase ST8SiaIV induction by teratogenic valproic acid analogs in F9 cell differentiation [21].
• By sequential immunoprecipitation and immunoblot analysis, phosphorylation of polysialyltransferase protein(s) was (were) demonstrated to occur on both serine and tyrosine residues and this was associated with decreased enzyme activity [22].
• Ouabain antagonists (PST 2238 and canrenone) and NCX blockers (SEA0400 and KB-R7943) normalize myogenic tone in ouabain-treated arteries [23].

Regulatory relationships of St8sia4

• These findings support in vitro evidence indicating PKCdelta to regulate polysialyltransferase activity and NCAM polysialylation state [22].

Other interactions of St8sia4

• These results indicate that ST8Sia II predominantly directs PSA expression during neuronal differentiation rather than ST8Sia IV [24].
• Our data reveal a complex polysialylation pattern and show that, under in vivo conditions, the coordinated action of ST8SiaII and ST8SiaIV is crucial to fine-tune the amount and structure of polySia on NCAM [10].
• The linage-specific sialidase treatment of glycoproteins as well as N-linked oligosaccharides from the glycoproteins revealed that ST8Sia IV exhibits an alpha2,8-sialytransferase activity toward alpha2,3-linked sialic acids of N-linked oligosaccharides [19].
• Moreover, a similar experimental approach revealed the degree of PKCdelta co-precipitation with polysialyltransferase protein(s) to be inversely correlated with polysialyltransferase activity [22].

Analytical, diagnostic and therapeutic context of St8sia4

• We used gene-targeting to generate mice lacking ST8SiaIV/PST-1, one of the polysialyltransferases responsible for addition of polysialic acid (PSA) to NCAM [9].
• Cloning and in situ hybridization analysis of the expression of polysialyltransferase mRNA in the developing and adult rat brain [25].
• A 39-mer oligonucleotide complementary to rat PST cDNA was synthesized to investigate the distribution of its mRNA in the developing and adult rat brain by Northern blot and in situ hybridization [25].
• In this chapter, we discuss methods used to analyze polysialyltransferase knockout mice using immunohistochemistry of brain and primary cultures of neurons [26].
• Our results supported that the piglet is a better animal model than other nonprimate species in the studies of ST8Sia IV related metabolism and nutrition in human infants [27].

References