Disease relevance of TNAP

• We have analyzed 16 missense mutations of the tissue-nonspecific AP (TNAP) gene found in patients with hypophosphatasia [1].
• Because abnormalities in PLP metabolism have been shown to cause epileptic seizures in mice null for the TNAP gene, these kinetic data help explain the variable expressivity of epileptic seizures in hypophosphatasia patients [1].
• Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis [2].

High impact information on TNAP

• We have identified a novel NIK interacting protein, TNAP (for TRAFs and NIK-associated protein) [3].
• Knockdown of TNAP by lentiviral-mediated small interference RNA potentiates TNF-alpha-induced NF-kappaB activation [3].
• 8. We also determined the ability of the mutants to metabolize two natural substrates of TNAP, that is, pyridoxal-5'-phosphate (PLP) and inorganic pyrophosphate (PPi), at physiological pH [1].
• After introducing each single hypophosphatasia mutation, the setTNAP and mutant TNAP cDNAs were expressed in COS-1 cells and the recombinant flagged enzymes were affinity purified [1].
• We have analyzed the role of the N-terminus and its microenvironment in determining the enzyme stability and catalysis using human placental (PLAP) and tissue-nonspecific AP (TNAP) as paradigms [4].

Biological context of TNAP

• In addition, retinoic acid plays an essential role in the superinduction of TNAP gene expression by enabling dexamethasone to exert its agonist activity, which otherwise has no effect [5].
• RESULTS: No difference was observed in the allele or genotype frequencies between patients and controls at either ENPP1 or TNAP [2].
• METHODS: Exons, untranslated regions (UTR) and exon-intron boundaries of ENPP1 and TNAP were sequenced using ABI Big Dye chemistry on automated sequencers [2].
• Sixteen variants were identified (3 in ENPP1 and 13 in TNAP) and were subsequently genotyped in 128 sporadic Caucasian CPPD CC patients and 600 healthy controls using a combination of polymerase chain reaction/restriction fragment-length polymorphism analysis or using Taqman [2].

Anatomical context of TNAP

• Expression of PHOSPHO1, like TNAP activity, was found to be up-regulated in MVs isolated from chondrocytes induced to differentiate by the addition of ascorbic acid [6].

Associations of TNAP with chemical compounds

• However, the ability of RU486 to antagonize the action of glucocorticoid was greatly compromised in dexamethasone-mediated superinduction of TNAP activity [5].
• Interestingly, TNAP was found to be the only isozyme activity superinduced when the cells were costimulated with retinoic acid and dexamethasone [5].

Other interactions of TNAP

• These data suggest that TNAP is a repressor of NIK activity and regulates both the classical and alternative NF-kappaB signaling pathways [3].

Analytical, diagnostic and therapeutic context of TNAP

• Site-directed mutagenesis was used to introduce a sequence tag into the TNAP cDNA and eliminate the glycosylphosphatidylinositol (GPI)-anchor recognition sequence to produce a secreted epitope-tagged TNAP (setTNAP) [1].
• Northern blot and RT-PCR analysis were then used to demonstrate that the steady-state TNAP mRNA level was also superinduced, which indicates that the superinduction is regulated at the transcriptional or post-transcriptional levels [5].

References