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Gene Review

RNF34  -  ring finger protein 34, E3 ubiquitin...

Homo sapiens

Synonyms: CARP-1, CARP1, Caspase regulator CARP1, Caspases-8 and-10-associated RING finger protein 1, E3 ubiquitin-protein ligase RNF34, ...
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Disease relevance of RNF34


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


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


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


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].


  1. Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer. Sasaki, S., Nakamura, T., Arakawa, H., Mori, M., Watanabe, T., Nagawa, H., Croce, C.M. Oncogene (2002) [Pubmed]
  2. Overexpression of hRFI (human ring finger homologous to inhibitor of apoptosis protein type) inhibits death receptor-mediated apoptosis in colorectal cancer cells. Konishi, T., Sasaki, S., Watanabe, T., Kitayama, J., Nagawa, H. Mol. Cancer Ther. (2005) [Pubmed]
  3. Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma-carcinoma sequence. Sasaki, S., Watanabe, T., Konishi, T., Kitayama, J., Nagawa, H. J. Exp. Clin. Cancer Res. (2004) [Pubmed]
  4. Different Z DNA forming sequences are revealed in phi X174 RFI by high resolution darkfield immuno-electron microscopy. Revet, B., Zarling, D.A., Jovin, T.M., Delain, E. EMBO J. (1984) [Pubmed]
  5. Purification and molecular cloning of a DNA ADP-ribosylating protein, CARP-1, from the edible clam Meretrix lamarckii. Nakano, T., Matsushima-Hibiya, Y., Yamamoto, M., Enomoto, S., Matsumoto, Y., Totsuka, Y., Watanabe, M., Sugimura, T., Wakabayashi, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. 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. Konishi, T., Sasaki, S., Watanabe, T., Kitayama, J., Nagawa, H. Oncogene (2006) [Pubmed]
  7. Effect of head-out water immersion on hepatorenal syndrome. Bichet, D.G., Groves, B.G., Schrier, R.W. Am. J. Kidney Dis. (1984) [Pubmed]
  8. Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. Tibbetts, M.D., Shiozaki, E.N., Gu, L., McDonald, E.R., El-Deiry, W.S., Shi, Y. Structure (Camb.) (2004) [Pubmed]
  9. Role of DNA gyrase in phiX replicative-form replication in vitro. Marians, K.J., Ikeda, J.E., Schlagman, S., Hurwitz, J. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  10. Specificity of the endonuclease activity of the baculovirus alkaline nuclease for single-stranded DNA. Mikhailov, V.S., Okano, K., Rohrmann, G.F. J. Biol. Chem. (2004) [Pubmed]
  11. Volume regulation in leukocytes: requirement for an intact cytoskeleton. Downey, G.P., Grinstein, S., Sue-A-Quan, A., Czaban, B., Chan, C.K. J. Cell. Physiol. (1995) [Pubmed]
  12. Multiple sclerosis-associated agent: transmission to animals and some properties of the agent. Koldovsky, U., Koldovsky, P., Henle, G., Henle, W., Ackermann, R., Haase, G. Infect. Immun. (1975) [Pubmed]
  13. hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated with 5-fluorouracil. Sasaki, S., Watanabe, T., Kobunai, T., Konishi, T., Nagase, H., Sugimoto, Y., Oka, T., Nagawa, H. Oncol. Rep. (2006) [Pubmed]
  14. Cell Cycle- and Apoptosis-regulatory Protein-1 Is Involved in Apoptosis Signaling by Epidermal Growth Factor Receptor. Rishi, A.K., Zhang, L., Yu, Y., Jiang, Y., Nautiyal, J., Wali, A., Fontana, J.A., Levi, E., Majumdar, A.P. J. Biol. Chem. (2006) [Pubmed]
  15. Differences in unwinding of supercoiled DNA induced by the two enantiomers of anti-benzo[a]pyrene diol epoxide. Xu, R., Birke, S., Carberry, S.E., Geacintov, N.E., Swenberg, C.E., Harvey, R.G. Nucleic Acids Res. (1992) [Pubmed]
  16. Process of infection with bacteriophage phi X 174 XXXVIII. Replication of phi chi 174 replicative form in vivo. Fukuda, A., Sinsheimer, R.L. J. Virol. (1976) [Pubmed]
  17. Identification of a novel human ankyrin-repeated protein homologous to CARP. Moriyama, M., Tsukamoto, Y., Fujiwara, M., Kondo, G., Nakada, C., Baba, T., Ishiguro, N., Miyazaki, A., Nakamura, K., Hori, N., Sato, K., Shomori, K., Takeuchi, K., Satoh, H., Mori, S., Ito, H. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
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