Disease relevance of REG1A

• Historically, PSP was discovered long before reg, yet, in many areas outside of the pancreatitis research field, reg is being used [1].
• REG Ialpha protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer [2].
• Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family [3].
• Pancreatic stone protein (PSP) is reported to be a key protein to form protein plugs in chronic pancreatitis [4].
• In the follow-up, the patients were diagnosed as having Parkinson's disease (PD, n = 25), dementia with Lewy bodies (DLB, n = 6), multiple system atrophy (MSA, n = 13), progressive supranuclear palsy (PSP, n = 8), corticobasal degeneration (CBD, n = 9), and essential tremor (ET, n = 11) [5].

Psychiatry related information on REG1A

• Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD) [6].
• Postural instability successfully classified PSP from Pick's disease [7].
• The motor skill task performance of the PD and PSP patients improved with training, but the improvement disappeared within a few months, whereas AD patients retained learned skills for 3-18 months [8].
• In contrast to the two cases previously reported by others, in which the preoperative TEPs were normal, the two cases reported herein showed significant changes on the affected side: the sensory thresholds were greater and the peak latencies of P19 and N28 were longer on the affected side than those on the normal side [9].
• We compared regional brain concentrations of CP and copper between subjects with Alzheimer's disease (AD, n = 12), Parkinson's disease (PD, n = 14), Huntington's disease (HD, n = 11), progressive supranuclear palsy (PSP, n = 11), young adult normal controls (YC, n = 6) and elderly normal controls (EC, n = 7) [10].

High impact information on REG1A

• The architecture of the active site of members of the protein tyrosine phosphatase (PTP) superfamily renders these enzymes sensitive to reversible oxidation and inactivation [11].
• Here, we present the set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase (PTP) families [12].
• Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain [13].
• One of these regulatory complexes, the 11S regulator (known as REG or PA28), stimulates proteasome peptidase activity and enhances the production of antigenic peptides for presentation by class I molecules of the major histocompatibility complex (MHC) [14].
• The reliable construction of evolutionary trees from nucleotide sequences often depends on randomization tests such as the bootstrap and PTP (cladistic permutation tail probability) tests [15].

Chemical compound and disease context of REG1A

• This study identifies retinoic acid (RA) as an inducer for Epo production in the embryonal carcinoma cell lines P19 and F9 [16].
• Embryonal carcinoma P19 cells produce erythropoietin constitutively but express lactate dehydrogenase in an oxygen-dependent manner [17].
• Culture medium conditioned by P19 embryonal carcinoma (EC) cells contains potent mitogenic activity which is markedly potentiated when the medium is conditioned in the presence of heparin [18].
• Immunohistochemistry for REG I protein was performed in 100 formalin-fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45 hepatolithiasis with ICC (n = 19) or biliary dysplasia (n = 26), 21 hepatolithiasis alone (all with hyperplasia), and 16 normal livers [19].
• Furthermore, hyperglycemia was found to inhibit protein tyrosine phosphatase (PTP) activity and increase phosphorylation of the tyrosine kinase Syk in platelets exposed to collagen [20].

Biological context of REG1A

• Comparisons of REG/PAP proteins between various species showed that the deduced amino acid sequences were conserved [21].
• By database searching and PCR analysis using a yeast artificial chromosome clone, the human REG family genes on chromosome 2, except for REG IV on chromosome 1, were mapped to a contiguous 140 kb region of the human chromosome 2p12 [22].
• Here we report the mapping of the REG gene to chromosome 2 using the polymerase chain reaction for the specific amplification of human reg sequences in rodent/human somatic cell hybrid DNA [23].
• A regional assignment has been made by in situ hybridization to metaphase chromosomes using two different fluorescently labelled genomic probes corresponding to the REG gene and a related gene REGL [23].
• A hitherto insufficiently understood phenomenon is the massive up-regulation of PSP/reg in pancreatic tissue and juice under conditions of stress [1].

Anatomical context of REG1A

• RESULTS: For PSP/reg, a role in proliferation and regeneration of islet cells has been postulated [1].
• The pancreatic stone protein and its secretory form (PSP-S) are inhibitors of CaCO3 crystal growth, possibly involved in the stabilization of pancreatic juice [24].
• A sensitive radioimmunoassay employing monoclonal antibodies against human pancreatic thread protein failed to detect the antigen in a wide range of human tissues other than pancreas, nor was the antigen measurable in normal human sera [25].
• The effects of cytokines on REG Ialpha promoter activity and its messenger RNA (mRNA) expression in AGS (a kind of gastric cancer cell line) cells were examined by luciferase reporter assay and Northern blot analysis, respectively [2].
• BACKGROUND & AIMS: Although a significant amount of regenerating gene (REG) Ialpha protein is present not only in normal gastric mucosa but also in gastric cancer tissues, its pathophysiologic role in gastric cancer development remains unclear [2].

Associations of REG1A with chemical compounds

• Effects of REG Ialpha protein on cell growth and H2O2-induced apoptosis in AGS cells were examined by 3,-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase nick-end labeling (TUNEL) assays, respectively [2].
• A glycoprotein expressed in exocrine pancreas (where it has been called lithostathine) and endocrine pancreas (where it has been called the regeneration protein) is encoded by a gene (REG) which maps to 2p12 [26].
• Among the eleven amino acids of the PSP S2-5 N-terminal extension Z-E-A-Q-T-E-L-P-Q-A-R, the first residue is an oxoproline and the fifth, a threonine, bears the single carbohydrate chain of the protein molecules [27].
• Variations in the glycan chain composition account for the differences in the Mr of PSP S2-5 [27].
• N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue [27].

Other interactions of REG1A

• RESULTS: REG Ialpha-positive early gastric cancers showed a significantly higher PCNA labeling index and more severe inflammatory cell infiltration in adjacent gastric mucosa than the negative cancers [2].
• Several of these are specifically expressed in pancreas, such as pancreatic amylase, pancreatic stone protein, pancreatitis-associated protein, pancreatic lipase, pancreatic elastase, etc [28].
• We identified by a monoclonal antibody-based immunoradiometric assay high concentrations of an exocrine pancreatic protein called pancreatic thread protein (PTP) in several areas of Alzheimer disease (AD) brain [29].
• The sequence of IX/X-bp showed 25-37% identity with that of the C-type carbohydrate recognition domain-like structure of acorn barnacle lectin, human and rat asialoglycoprotein receptors, the human lymphocyte Fc epsilon receptor for immunoglobulin E, proteoglycan core protein, pancreatic stone protein, and tetranectin [30].
• The amino-terminal domain of thrombomodulin and pancreatic stone protein are homologous with lectins [31].

Analytical, diagnostic and therapeutic context of REG1A

• Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III [22].
• METHODS: Early gastric cancer specimens were analyzed histologically using immunohistochemistry for REG Ialpha protein and proliferating cell nuclear antigen (PCNA) [2].
• Transcripts for the REG gene were found in 53% of colorectal cancers and for the PAP gene in 60% of colorectal cancers, by RT-PCR [3].
• RESULTS: Using RT-PCR and Western blot analyses, reg mRNA and 16-kilodalton REG proteins were detected in two of eight human gastric carcinoma cell lines [32].
• Overall and disease-free survival were found to be poor for patients with REG-positive tumors [33].

References