Disease relevance of TALDO1

• Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis [1].
• Presence of crossreactive antigenic epitopes between recombinant TAL-H and HTLV-I/human immunodeficiency virus type 1 (HIV-1) gas proteins was demonstrated by Western blot analysis [1].
• Remarkable amino acid sequence homologies were noted between TAL-H and core proteins of human retroviruses [1].
• Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway [2].
• Immunohistochemical studies of postmortem brain sections revealed decreased staining by MBP- and TAL-specific antibodies in MS plaques, indicating a concurrent loss of these antigens from demyelination sites [3].

High impact information on TALDO1

• Based on homology to human T cell lymphotropic virus type I (HTLV-I) a novel human retrotransposon was cloned and found to constitute an integral part of the coding sequence of the human transaldolase gene (TAL-H) [1].
• In addition, recombinant TAL-H stimulated proliferation and caused aggregate formation of peripheral blood lymphocytes from patients with MS [1].
• Immunohistochemical analyses of human brain sections and primary murine brain cell cultures demonstrated that TAL is expressed selectively in oligodendrocytes at high levels, possibly linked to production of large amounts of lipids as a major component of myelin, and to the protection of the vast network of myelin sheaths from oxygen radicals [1].
• Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis [3].
• TAL(-/-) spermatozoa show loss of Deltapsi(m) and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH [4].

Chemical compound and disease context of TALDO1

• Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca(2+) levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and gamma-glutamyl transferase [4].
• Stimulation of de novo GSH synthesis by oral N-acetyl-cysteine normalized the low fertility rate of TAL(+/-) males without affecting the sterility of TAL(-/-) males [4].
• Recombinant transaldolase from Escherichia coli, an enzyme of the pentose phosphate pathway has been crystallized by the vapor-diffusion method using polyethylene glycol 6000 as precipitant [5].

Biological context of TALDO1

• Fluorescence in situ hybridization with a 15-kb genomic fragment harboring exons 1 and 2 mapped TALDO1 to 11p15.4-p15 [6].
• The human transaldolase gene (TALDO1) is located on chromosome 11 at p15.4-p15.5 [6].
• Reverse transcriptase-PCR studies of human-mouse somatic cell hybrids revealed the presence of the functional TAL-H gene on chromosome 11 and its absence on human chromosome 1 [6].
• 5. A truncated and mutated segment of TAL-H exon 5 terminating with a poly(A) tail was identified in a pseudogene locus (TALDOP1) on chromosome 1 [6].
• Transaldolase regulates redox-dependent apoptosis through controlling NADPH and ribose 5-phosphate production via the pentose phosphate pathway [7].

Anatomical context of TALDO1

• DNase I footprinting with nuclear extracts of transaldolase-expressing cell lines unveiled protection of nucleotides -29 to -16 [7].
• ZNF143 and transaldolase expression correlated in 21 different human tissues and were coordinately upregulated 14- and 34-fold, respectively, in lactating mammary glands compared with nonlactating ones [7].
• The results suggest that molecular mimicry between viral core proteins and TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS [1].
• High-affinity autoantibodies to recombinant TAL-H were detected in serum (25/87) and cerebrospinal fluid (15/20) of patients with MS [1].
• By incubating the patient's lymphoblasts and erythrocytes with ribose-5-phosphate and subsequently analyzing phosphate sugar metabolites, we discovered a deficiency of transaldolase [2].

Associations of TALDO1 with chemical compounds

• Transaldolase (TAL) is a key enzyme of the pentose phosphate pathway, which is responsible for generation of reducing equivalents to protect cellular integrity from reactive oxygen intermediates [6].
• The minimal promoter sufficient to drive chloramphenicol acetyltransferase reporter gene activity was mapped to nucleotides -49 to -1 relative to the transcription start site of the human transaldolase gene [7].
• In blood from the TALDO1-deficient patient, sedoheptulose 7-phosphate was increased [8].
• DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G>A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H) [9].
• This deletion results in absence of serine at position 171 of the transaldolase protein [2].

Physical interactions of TALDO1

• Transaldolase is part of a supramolecular complex containing glucose-6-phosphate dehydrogenase in human neutrophils that undergoes retrograde trafficking during pregnancy [10].

Other interactions of TALDO1

• Chromatin immunoprecipitation studies confirm that ZNF143/73 associates with the transaldolase promoter in vivo [7].
• Electrophoretic mobility shift assays identified a single dominant DNA-protein complex that was abolished by consensus sequence for transcription factor ZNF143/76 or mutation of the ZNF76/143 motif within the transaldolase promoter [7].
• Human transaldolase-associated repetitive elements are transcribed by RNA polymerase III [11].
• Human transaldolase has been implicated as an autoantigen in multiple sclerosis and four immunodominant peptide segments are located at the surface of the enzyme, accessible to autoantibodies [12].
• Since mitochondrial ROI levels are regulated by the supply of NADPH from the pentose phosphate pathway (PPP), the effect of transaldolase (TAL), a key enzyme of PPP, was investigated [13].

Analytical, diagnostic and therapeutic context of TALDO1

• Mapping of radiation hybrids placed TALDO1 between markers WI-1421 and D11S922 on 11p15 [6].
• Southern blot hybridization of a 827-bp 3' EcoRI fragment of the TAL-H cDNA to human-mouse somatic cell hybrid DNA localized TALDO1 to the p13-->pter region of chromosome 11 [6].
• Sequence analysis of the transaldolase gene from this patient showed a homozygous deletion of 3 bp [2].
• Reverse transcriptase-polymerase chain reaction and in vitro transcription analyses showed that transcription of TARE-6 proceeded in the orientation of the RNA pol III promoter of the Alu dimer and opposite to the orientation of the TAL-H gene [11].
• Structure-based sequence alignment of available sequences of the transaldolase subfamily reveals that eight active site residues are invariant in the whole subfamily [12].

References