Disease relevance of NPAT

• NPAT is mutated in Hodgkin lymphoma [1].
• Ataxia-telangiectasia and T-cell leukemias: no evidence for somatic ATM mutation in sporadic T-ALL or for hypermethylation of the ATM-NPAT/E14 bidirectional promoter in T-PLL [2].
• The MFCV of a patient with myotonic dystrophy was also studied, and it was suggested that the NPAT would be clinically useful [3].
• The NPAT was measured in 14 gallbladder bile samples derived from patients with cholesterol gallstones and 9 controls [4].

High impact information on NPAT

• OCA-S also interacts with NPAT, a cyclin E/cdk2 substrate that is broadly involved in histone gene transcription [5].
• NPAT interacts with CDK9 to control replication-dependent histone mRNA 3' end processing in human cells [6].
• Thus, our results both show that NPAT is involved in a key S phase event and provide a link between the cell cycle machinery and activation of histone gene transcription [7].
• Inhibition of Cdk2 activity by specific inhibitors in the absence of DNA damage similarly disperses NPAT from histone gene clusters and represses histone gene expression [8].
• The inhibition of NPAT expression by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells [9].
• We identified a new gene, designated NPAT, from the major AT locus on human chromosome 11q22-q23 [10].

Biological context of NPAT

• The structure and organization of NPAT were determined by direct sequencing of cosmid clones carrying the gene and by application of the long and accurate (LA)-PCR method to amplify regions encompassing the exon/intron boundaries and all of the exons [11].
• Recently we found that another housekeeping gene, NPAT, is located upstream of ATM on human chromosome 11 [11].
• To investigate whether these sequences are effective for nuclear transport of NPAT, an NPAT-green fluorescent protein fusion (NP-GFP) was constructed [12].
• After transfection of the fusion gene containing the full coding region of NPAT into cultured cells, the NP-GFP product was found exclusively in the nucleus [12].
• Our results thus suggest that inhibition of Cdk2 activity following DNA damage results in the downregulation of histone gene transcription through dissociation of NPAT from histone gene clusters [8].

Anatomical context of NPAT

• ZPR1 deficiency causes disruption of survival motor neurons and NPAT localization within the nucleus, blocks S phase progression, and arrests cells in both the G(1) and G(2) phases of the cell cycle [13].
• Partial rigid-body dynamics in NPT, NPAT and NPgammaT ensembles for proteins and membranes [14].

Associations of NPAT with chemical compounds

• To investigate the possibility of nonmutational or nonrecombinational mechanisms of T-PLL development, we have used bisulfite genomic sequencing to analyze DNA methylation in the putative bidirectional promoter region of the closely linked ATM and NPAT/E14 genes within the CpG island at 11q22-q23 [2].

Other interactions of NPAT

• Moreover, we show that the expression of NPAT accelerates S-phase entry in cells released from quiescence [9].
• As predicted from these changes, trastuzumab decreased the DNA-binding activity of E2F, decreased the level of NPAT protein, and decreased the level of histone H4 mRNA [15].

Analytical, diagnostic and therapeutic context of NPAT

• For investigation of the role of NPAT in AT and these tumors with allelic loss of 11q22-q24, appropriate primer sequences and PCR conditions for amplification of all the NPAT exons from genomic DNA were determined [11].

References