Disease relevance of REEP5

• The murine homolog of TB2/DP1, a gene of the familial adenomatous polyposis (FAP) locus [1].
• These 2 proteins colocalized in mitochondria but the expression of HCCR-1 showed negative correlation with that of DP1 in colorectal cancer (CRC) [2].
• Intra-articular injection of DP1 and DP2 into arthritic rabbit joints with synovial hyperplasia induced extensive apoptosis of the hyperplastic synovium, while reducing the leukocytic infiltration and synovitis [3].
• Furthermore, there is in vivo evidence that PGD2 contributes to allergen-induced pulmonary eosinophilia via its classic DP1 receptor [4].
• Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis [5].

High impact information on REEP5

• The second, provisionally designated DP1 (deleted in polyposis 1), was found to be transcribed in the same orientation as MCC [6].
• Loss of heterozygosity frequency around DP1 also was examined [2].
• DP1 played a tumor-suppressor role in colon tumorigenesis (ie, DP1-transfected RKO cells showed growth inhibition, apoptosis, decreased telomerase activity, and up-regulation of p53) [2].
• By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD(2)- and NA-induced vasodilation [7].
• Our data do not indicate that selection operated at I1307K (D5S346, P=.114; D5S135, P=.373), providing compelling evidence that the high frequency of disease-susceptibility alleles in the Ashkenazim is due to genetic drift, not selection [8].

Chemical compound and disease context of REEP5

• These results suggested that prostaglandin D2 plays a physiological role in inhibiting pruritis of NC/Nga mice via their specific prostanoid DP1 receptors, and that prostaglandin D2 and/or a prostanoid DP1 receptor agonist may have therapeutic effects for cases of consecutive skin inflammation [5].
• Using a murine model of atopic dermatitis, a chronic Th2-type allergic inflammatory disease, we demonstrate that the potent DP1 agonist BW245C dramatically decreases the Ag-specific T cell activation in the skin draining lymph nodes and markedly prevents the skin lesions following repeated epicutaneous sensitization with OVA [9].
• Pemphigus blister fluid was distinguished by high IL-1-like activity, proteolytic activity, and high concentrations of TB2 and LTB4, while pemphigoid blister fluid was characterized by higher IL-2-like activity, antiprotease activity, and high PGE2 concentration [10].
• The aim of the present study was to investigate the loss of heterozygosity (LOH), mainly at tumour suppressor loci (using markers D1S2883, D2S123, D3S1611, D5S346, D7S501, D8S254, TP53, NM23), microsatellite instability (BAT25, 26, 40) and <hidden chromosome instability> (bleomycin test) in patients with squamous cell larynx cancer [11].

Biological context of REEP5

• We report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene [12].
• E2F binds to DNA as homodimers or as heterodimers in association with a protein, DP1 (for dimerization partner 1) [13].
• RESULTS: Marker D5S346, located 30 to 70 kilobases from the APC locus, showed evidence highly suggestive of linkage to the disease phenotype (lod score = 1.92) [14].
• LOH on 5q was present in 2 of 6 (33.3%) informative cases, and both cases showed LOH on the D5S346 marker, a microsatellite marker near the APC locus [15].
• We screened DNA extracted from this specimen with dinucleotide repeat (CA/GT)n polymorphic marker (D5S346) linked to the adenomatous polyposis coli gene and established that the proband is at more than 99% risk of developing FAP [16].

Anatomical context of REEP5

• Triggering of murine mast cells by IgE plus antigen results in a decrease of TB2/DP1 mRNA up to 60% after 2 h implying a possible role of this gene in regulation of the allergic effector cell [1].
• The balance between DP1 and DP2 receptors could determine the degree to which prostaglandin D2 can activate eosinophils and may play a role in eosinophil recruitment in asthma [17].
• Unlike DP1, there appear to be multiple transcripts for DP2 and their distribution appears to vary in different tissues and cell lines [13].
• METHODS AND RESULTS: DNA extracted from 28 paired blood and formalin-fixed, paraffin-embedded normal mucosal tissue was amplified using the DP1 microsatellite marker, consisting of a variable number of CA repeats [18].
• DP1 receptor transcripts were present only in HT-29 cells [19].

Associations of REEP5 with chemical compounds

• Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats [4].
• On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, polyacrylamide gel isoelectric focusing and amino acid analysis, both DP1 and DP2 were demonstrated to have close physicochemical similarity with DF1 and DF2, respectively [20].
• In cells prelabeled with [14C] arachidonic acid, phytohemagglutinin (PHA) produced substantial (3.5- to 12-fold) increases in 5-HETE, 12-HETE, and TB2 radiolabeling [21].
• Binding to TB2 was ablated by the presence of N-terminal domains (encoded by exons 1-8) and reduced after deleting the proline-rich region [22].
• DES in the diet reduced and testosterone injections elevated relative prostate weights and perimeters of the dorsal, LP1, lateral prostate type 2 and DP1 expression [23].

Other interactions of REEP5

• We report on a family with a submicroscopic deletion of about 200 kb including more than the 3' half of the APC gene and the adjacent DP1 gene [24].
• Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49 [25].
• Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively [26].
• Polymerase chain reaction using four APC microsatellite markers-D5S210, D5S299, D5S82, and D5S346-was performed and the products analysed [27].
• METHODS: We examined 104 invasive ovarian cancers for MSI with six microsatellite markers (BAT25, BAT26, D5S346, D2S123, D17S250 and NME1) [28].

Analytical, diagnostic and therapeutic context of REEP5

• Although the APC markers (D5S210, D5S346, D5S299, and D5S82) tested did show an overall high frequency of allelic imbalance/loss of heterozygosity (62.48%) and microsatellite instability (41.27%), they did not show prognostic significance in the study cohort and were not correlated with the immunohistochemical data [29].
• DP2 subjects showed AMP and CV values significantly lower than those in DP1 subjects, and signs of acute and chronic denervation/reinervation were found in the leg muscles [30].
• Furthermore, direct injection of DP1 into day 7 established MCA205 tumors in C57BL/6 mice resulted in the induction of tumor apoptosis and subsequent reduction in tumor volume [31].
• These results suggest that DP1 may be used clinically to treat accessible solid tumors or as an adjuvant therapy in conjunction with radiotherapy, standard chemotherapy, immunotherapy, or surgical debulking [31].
• In immunofluorescence microscopy DP1 reacts with desmosomes in epithelial cells from a variety of human tissues including skin, esophagus, uterus, intestine, and in liver hepatocytes [32].

References