Disease relevance of APEH

• The use of specific somatic cell hybrids have allowed us to locate the YAC contig telomeric to the D3F15S2 locus, in a region which is frequently deleted in lung carcinomas [1].
• A gene near the D3F15S2 site on 3p is expressed in normal human kidney but not or only at a severely reduced level in 11 of 15 primary renal cell carcinomas (RCC) [2].
• The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer [3].
• In summary, the 3p chromosome region near the D3S3 locus (3p12-p13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D3S2 (3p14-p21.1), D3F15S2 (3p21), and THRB (3p24) loci [4].
• In addition to D3S3, the lowest frequencies of heterozygosity were seen at D3F15S2 for Ad (9%), D3S2 for large cell carcinomas (8%), and THRB for adenosquamous (0%), bronchioloalveolar (0%), and large cell (8%) carcinomas [4].

Psychiatry related information on APEH

• Best sensitivity and response time were obtained with sensors prepared with 250 U of OPH and measuring at 37 degrees C in 1.0 mM HEPES buffer, pH 9.3, containing 100 mM NaCl [5].

High impact information on APEH

• The constitutional heterozygosity for the DNF15S2 locus and for one allele of the c-erbA beta and the c-raf-1 proto-oncogenes was lost in nonpapillary RCCs, whereas both alleles were retained in each papillary RCC analyzed [6].
• An 87% identity has been found between the reported cDNA sequence that encodes acylpeptide hydrolase (EC 3.4.19.1) [Mitta, M., Asada, K., Uchimura, Y., Kimizuka, F., Kato, I., Sakiyama, F. & Tsunasawa, S. (1989) J. Biochem. 106, 548-551] and a cDNA transcribed from a locus (DNF15S2) on the short arm of human chromosome 3, reported by Naylor et al [7].
• [Naylor, S.L., Marshall, A., Hensel, C., Martinez, P.F., Holley, B. & Sakaguchi, A.Y. (1989) Genomics 4, 355-361]; the DNF15S2 locus suffers deletions in small cell lung carcinoma associated with a reduction or loss of acylase activity (EC 3.5.1.14) [7].
• Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNF15S2 than to ERBA beta and is almost certainly not the latter [8].
• This sequence is the first described that can regulate a basal promoter in response to starvation for several individual amino acids and therefore can be called an amino acid response element (AARE) [9].

Chemical compound and disease context of APEH

• Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid-beta peptide [10].
• A chimeric vector pKR612B1 was developed containing the neomycin phosphotransferase (APH) gene from the Tn5 transposon under the control of the gene VI promoter of cauliflower mosaic virus (CaMV), and was used to transform higher plant protoplasts [11].
• In this paper, we reported the construction of a hybrid biosensor for direct, highly selective, sensitive, and rapid quantitative determination of organophosphate pesticides with p-nitrophenyl substituent using purified organophosphorus hydrolase (OPH) for the initial hydrolysis and Arthrobacter sp. JS443 for subsequent p-nitrophenol oxidation [12].
• OPH catalyzed the hydrolysis of organophosphorus pesticides with p-nitrophenyl substituent such as paraoxon and methyl parathion to release p-nitrophenol that was oxidized by the enzymatic machinery of Arthrobacter sp. JS443 to carbon dioxide through electroactive intermediates 4-nitrocatechol and 1,2,4-benzenetriol [12].
• These findings suggest that for E. coli resistant to both ampicillin and an AG, APH enzymes are the predominant AME class [13].

Biological context of APEH

• More recently we have identified a putative CpG island in the vicinity of D3F15S2, suggesting that DNA sequences in or around this site may have coding potential (Boldog, F., Erlandsson, R., Klein, G. & Sümegi, J. (1989). Cancer Genet. Cytogenet., 42, 295-306) [2].
• A gene that corresponds to the most frequently lost RFLP site (D3F15S2) is expressed in a variety of human tissues, and at a particularly high level in the kidney [14].
• The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 has led to the isolation of several cDNA clones [2].
• Of the 23 tumors informative for D3F15S2, one showed LOH [15].
• One SCLC cell line, H748, has an interstitial deletion of chromosome 3p and shows allele loss for the DNF15S2 locus detected by the probe lambda H3 [3].

Anatomical context of APEH

• Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase [16].
• We did not detect changes in the level of binding of this factor to the AARE by using nuclear extracts from HeLa cells grown under starved conditions, suggesting that activation of this factor(s) results from posttranslational modification or complexing with other proteins that do not affect its DNA-binding properties [17].
• Both the nucleus of the basal optic root (nBOR) and nucleus lentiformis mesencephali of the AOS were shown to project to the area ventralis of Tsai (AVT), which in turn was shown to project to the Hp/APH [18].
• Furthermore, AS NSRE-2 can confer endoplasmic reticulum stress responsiveness to the CHOP AARE [19].
• None of the informative thyroid tumors studied had allelic loss detected with probes for chromosome 2q (D2S44), 3p (D3F15S2, D3S32), 3q (D3S46), 4p (D4S125), 6p (D6S40), 8q (D8S39), 9q (D9S7), 12p (D12S14), 13q (D13S52), 17p (D17S30), or 18q (D18S10) [20].

Associations of APEH with chemical compounds

• Sequence analysis indicated that the DNF15S2 locus could potentially code for a previously unreported protein of 67 kDa which has 26 cysteine residues [3].
• As well as the enzyme activities of OPH, those of rACPH were inhibited by DFP [16].
• OPH showed ACPH activity when N-acetyl-L-alanine p-nitroanilide and N-acetylmethionyl L-alanine were used as substrates [16].
• To lift the OPH from the solid substrate, a pair of polyelectrolytes (positively charged chitosan (CS) and negatively charged poly(thiophene-3-acetic acid) (PTAA)) were combined [21].
• Homocysteine regulates expression of Herp by DNA methylation involving the AARE and CREB binding sites [22].

Other interactions of APEH

• This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity [15].
• In 18 matched carcinoma specimens, LOH (deletion) was observed at D3S32 in 0 of 7, at D3F15S2 in 9 of 12 (75%), and at THRB in 3 of 9 cases (33%) [23].
• This group is unrelated to the classical trypsin and subtilisin families, and includes dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B, in addition to the prototype prolyl oligopeptidase [24].

Analytical, diagnostic and therapeutic context of APEH

• We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24) [4].
• Six peptide fragments of OPH obtained by digestion of DFP-labeled OPH with lysyl endopeptidase were isolated by use of reverse-phase high-performance liquid chromatography, and the sequence of more than eight amino acids from the N-terminal position of each peptide was determined [16].
• From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription [25].
• Electrophoretic mobility shift assay and transient transfection experiments show that several transcription factors that belong to the C/EBP or ATF families bind the AARE sequence and activate transcription [26].
• A method is described for the identification of the aminoglycoside-phosphorylating (APH) enzymes APH(2'') and APH(3') by the high performance liquid chromatographic (HPLC) identification of their products of reaction with kanamycin and ATP [27].

References