Disease relevance of RNF34

• Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer [1].
• However, the function role of hRFI in colorectal carcinoma has not been elucidated [2].
• Although all normal colorectal glands and most hyperplastic polyps (71.4%) showed no staining of hRFI, most colorectal adenomas and carcinomas (93.2%) showed a focal or diffuse staining (P<0.001) [3].
• Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma-carcinoma sequence [3].
• Immunohistochemical staining was performed on 48 colorectal carcinomas and 77 colorectal polyps consisting of 70 adenomas and 7 hyperplastic polyps using the antibody of hRFI [3].

High impact information on RNF34

• Z DNA sequences in phi X174 RFI DNA were mapped [4].
• CARP-1 in the culture medium showed no cytotoxicity against HeLa and TMK-1 cells; however, introduction of this protein by electroporation induced apoptosis in these cells [5].
• Neither the nucleotide nor the deduced amino acid sequence of CARP-1 showed homology with pierisin-1 or -2 [5].
• However, a glutamic acid residue (E128) at the putative NAD-binding site, conserved in all ADP-ribosyltransferases, was found in CARP-1, and replacement of aspartic acid for this glutamic acid resulted in loss of almost all ADP-ribosylating activity [5].
• The protein synthesized in vitro from the cDNA in a reticulocyte lysate exhibited the same ADP-ribosylating activity as that of purified CARP-1 [5].

Chemical compound and disease context of RNF34

• Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal cancer cells via activation of NF-kappaB and upregulation of BCL-2 and BCL-XL [6].
• Human Ring-Finger homologous to Inhibitor of apoptosis protein type (hRFI) is a newly discovered gene that has been shown to inhibit death receptor-mediated apoptosis in colorectal cancer cells [6].
• A 47-year-old patient with severe decompensated alcoholic liver disease developed a progressive deterioration of her renal function (serum creatinine 4.0 mg/dL) with a renal failure index (RFI: UNa/U/PCr) consistently less than 1 [7].

Biological context of RNF34

• HeLa cells transfected with hRFI construct exhibited a tendency to resist TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of the hRFI product [1].
• The caspase-associated ring proteins (CARP1 and CARP2) are distinguished from other caspase regulators by the presence of a FYVE-type zinc finger domain [8].
• We also established an antisense down-regulation of hRFI, which effectively reversed the antiapoptotic activity of the hRFI transfectant [2].
• After exposure to preparations of DNA gyrase, the relaxed phiX174 replicative form is converted to phiX RFI which can then be attacked by the phiX gene A protein and participate in replication of duplex phiX DNA [9].
• The AN endonuclease showed specificity for single-stranded DNA and converted supercoiled plasmid DNA (replicative form I, RFI) into the open circular form (RFII) by a single strand break [10].

Anatomical context of RNF34

• A 2.0 kb hRFI transcript was ubiquitously expressed in all human tissues as well as several cancer cell lines examined [1].
• Immunohistochemistry has revealed that the expression of hRFI increased in transition from normal colorectal mucosas to adenomas and from adenomas to carcinomas, suggesting an essential role in the early stage of colorectal carcinogenesis [2].
• Pretreatment with CB or CD resulted in profound actin disassembly in Jurkat cells (relative fluorescence index RFI: 1.0 control vs. 0.21 +/- 0.01 for CB and 0.48 +/- 0.02 for CD) [11].
• In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs [12].
• hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil [13].

Associations of RNF34 with chemical compounds

• CARP-1 is a tyrosine-phosphorylated protein, and ERRP treatments cause elevated tyrosine phosphorylation of CARP-1 [14].
• CARP-1, a novel apoptosis inducer, regulates apoptosis signaling by diverse agents, including adriamycin and growth factors [14].
• Treatments of cells with ERRP or Iressa (an EGFR tyrosine kinase inhibitor) results in elevated CARP-1 levels, whereas antisense-dependent depletion of CARP-1 causes inhibition of apoptosis by ERRP [14].
• The unwinding of supercoiled phi X174 RFI DNA induced by the tumorigenic (+) and non-tumorigenic (-) enantiomers of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) has been investigated by agarose slab-gel and ethidium titration tube gel electrophoresis [15].
• This DNA is observed at a position of greater density in a propidium diiodide-cesium chloride buoyant density gradient than normal RFI [16].

Other interactions of RNF34

• For colorectal carcinomas as well as colonic polyps we investigated the expression of a newly discovered gene, hRFI, which is isolated by the yeast two-hybrid screening using hTid as a bait and expressed highly in esophageal carcinomas [3].

Analytical, diagnostic and therapeutic context of RNF34

• Northern blot analysis showed that in 70% (14 out of 20) of esophageal cancer patients, expression of hRFI in cancerous regions was two or more times higher than in the corresponding normal tissues [1].
• Different Z DNA forming sequences are revealed in phi X174 RFI by high resolution darkfield immuno-electron microscopy [4].
• Purification and molecular cloning of a DNA ADP-ribosylating protein, CARP-1, from the edible clam Meretrix lamarckii [5].
• Overexpression of hRFI in SW480 and COLO320 colorectal cancer cells similarly resulted in resistance to 5-FU with the activation of NF-kappaB and upregulation of Bcl-2 and Bcl-XL. hRFI might be a novel therapeutic target for gene therapy in colorectal cancer [6].
• Protein sequence analysis revealed that Arpp is homologous (52.7% identity) to Carp which is shown to be involved in the regulation of the transcription of the cardiac ventricular myosin light chain 2 gene [17].

References