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Gene Review

AGO2  -  argonaute RISC catalytic component 2

Homo sapiens

Synonyms: Argonaute RISC catalytic component 2, Argonaute2, EIF2C2, Eukaryotic translation initiation factor 2C 2, PAZ Piwi domain protein, ...
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Disease relevance of EIF2C2

  • Although 15-minute skin reactions to schistosomal antigens remained unchanged, niridazole reduced or ablated positive 48-hour skin reactions to tuberculin (PPD), mumps and schistosome antigens in all patients tested six and 15 days after therapy began [1].
  • The PCA response was antigen specific: peripheral blood mononuclear cells (PBM) from donors sensitive to PPD or tularemia showed an increase in PCA only in response to the sensitizing antigen [2].
  • Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02) [3].
  • The reduction of Q10 by mammalian TrxR1 was selenium dependent as revealed by comparison with Escherichia coli TrxR or selenium-deprived mutant and truncated mammalian TrxR forms [4].
  • The patient was a 68-yr-old woman with hypo-gamma-globulinemia (IgM: 31 mg/dl, IgG: 223 mg/dl, IgA: 23 mg/dl); she suffered from cryptococcal meningitis and pulmonary tuberculosis with a negative result of skin tests to PPD and cryptococcal antigen [5].
  • These data indicate that Ago2 is regulated at both the transcriptional and posttranslational level, and also implicate Ago2 and enhanced micro-RNA activity in the tumorigenic progression of breast cancer cell lines [6].

Psychiatry related information on EIF2C2

  • Male gender (P<0.001), serum cholesterol (P<0.001), serum gamma-glutamyltransferase (P<0.001), serum triglycerides (P< 0.001), age (P=0.017) and 4-day alcohol consumption (P=0.03) were the most important factors which were directly associated with plasma Q10) [7].
  • The literature allows no firm conclusions about the significance of Q10 in physical activity [8].
  • The response time was also temperature-dependent, with a Q10 of about 2 [9].
  • We measured caudate volumes on pre- and post-treatment MRI scans from 19 patients at two sites who were participating in CARE-HD (Co-enzyme Q10 and Remacemide: Evaluation in Huntington's Disease), a 30-month clinical trial of remacemide and co-enzyme Q(10) in symptomatic patients with HD [10].
  • Statins although they may affect Co-enzyme Q10 levels in the body and the brain, do not worsen PD at least as assessed by stage, and prevalence of wearing-off, dyskinesia, and dementia [11].

High impact information on EIF2C2

  • PPD-induced lymphocyte transformation was severely depressed in three and partially depressed in two of the five patients [1].
  • The Dicer nuclease produces mature miRNAs and siRNAs from pre-miRNAs and double-stranded RNA (dsRNA), respectively, and associates with Ago2 [12].
  • Human Argonaute2 (hAgo2) was shown to be responsible for target RNA cleavage ("Slicer") activity in RNA interference (RNAi), whereas other Argonaute subfamily members do not exhibit the Slicer activity in humans [13].
  • Purification of the FLAG/HA-epitope-tagged Ago containing complexes from different human cell lines revealed that endonuclease activity is exclusively associated with Ago2 [14].
  • PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors [15].

Chemical compound and disease context of EIF2C2

  • On the basis of the phylogenetic positioning of the strains, DNA reassociation studies, phenotypic tests and the presence of the Q10 ubiquinone, this new species was assigned to the genus Gluconacetobacter [16].
  • Coenzyme Q10 (Q10) is available as an over-the-counter dietary supplement in the United States. While its use could be considered a form of alternative therapy, the medical profession has embraced the use of Q10 in specific disease states, including a series of neurologic and muscular diseases [17].
  • RESULTS: All the adjuvants were effective in inhibiting the development of allergen-induced airway eosinophilia, mucous production and, with the exception of PPD, also airway hyper-reactivity, when they were applied together with OVA/alum [18].
  • We conclude that 1) insensitivity to hypoxia indicates that rhythmic discharge does not reflect gasping behavior, 2) increased temperature alters respiratory discharge, and 3) central pH/CO2 sensitivity is unaffected by temperature in this preparation (i.e., Q10 approximately 1.0) [19].
  • Human PBMC were stimulated by tetanus toxoid (TT) or tuberculin (PPD) for 6 days and then pulsed with ionomycin and phorbol myristate acetate (PMA) for 24 h [20].

Biological context of EIF2C2

  • The up-regulation upon Ago2 and Dicer knock-downs was moderate and we found no evidence, at the mRNA level, for activation of silenced genes [21].
  • Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies [22].
  • We demonstrated that the anti-Ago2 monoclonal antibody 4F9 recognized GWBs in a cell cycle dependent manner and was capable of capturing miRNAs associated with Ago2 [23].
  • Finally, exogenous expression of hGERp95/EIF2C2/hAgo2, a human Ago1 homolog implicated in posttranscriptional gene silencing, compensated for the loss of ago1+ function in S. pombe [24].
  • However, over the last 2 years, great strides have been made towards elucidating how PPD proteins and Dicer regulate gene-silencing at the pre- and post-transcriptional levels [25].

Anatomical context of EIF2C2

  • The association in the cytosol of exported (mt) tRNA(Met) with Ago2 complements genetic and microscopic data that link mitochondria with RNAi-related components and events [26].
  • Various exported (mt) tRNAs were detected in the cytosol of 293 cells, but Ago2 was found selectively bound to (mt) tRNA(Met) [26].
  • 1 of 4 clones tested was able to mediate an increase in monocyte procoagulant activity (PCA) in response to PPD [27].
  • Among them, SMP-IV and MAP phosphatase, which can dephosphorylate intact smooth muscle myosin, showed extremely high Q10 values (5.3 and 5.2, respectively) [28].
  • The PPD-reactive gamma delta cells, when their receptors have been characterized, have been found to express a V gamma 9+ chain [29].

Associations of EIF2C2 with chemical compounds

  • PPD (PAZ Piwi domain) proteins and the Dicer family have been the subjects of intense study over the last 6 years [25].
  • Lysosomal cysteine uptake displays a Km of 0.05 mM at pH 7.0 and an activation energy of 21 kcal/mol, corresponding to a Q10 of 3 [30].
  • 2. The long delay (1.5 at 22 degrees C) following activation of alpha 1-adrenergic receptors through photolysis of caged phenylephrine and the high Q10 of this process are consistent with the hypothesis that activation of phospholipase C is the major mechanism of alpha-adrenergic pharmacomechanical Ca2+ release [31].
  • The microbial degradation of ethylenethiourea is highly temperature dependent with aerobic Q10 between 2.9 and 4.2, and an anaerobic between 2.1 and 2 [32].
  • Our results suggest that Q10 expression in liver depends upon RA and the interaction between nuclear receptors that are expressed in this organ [33].

Physical interactions of EIF2C2

  • In vitro reconstitution assays demonstrated that TRBP is required for the recruitment of Ago2 to the small interfering RNA (siRNA) bound by Dicer [34].

Other interactions of EIF2C2

  • Here we show that PAZ domains are not required for PPD protein-Dicer interactions [35].
  • To gain insight into the function and composition of RNA silencing complexes, we purified Ago1- and Ago2-containing complexes from human cells [36].

Analytical, diagnostic and therapeutic context of EIF2C2

  • Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients [15].
  • When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables [3].
  • The heterogeneity (Q10 = 57.7, P<.001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study [37].
  • Their tear proteins were analyzed using SELDI-TOF-MS ProteinChip Arrays with three different chromatographic surfaces (CM10 cation exchange, Q10 anion exchange, and H50 reversed-phase) prepared by means of a laboratory liquid-handling robotic workstation [38].
  • Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle, and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard [39].


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  3. A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer. Badalament, R.A., Herr, H.W., Wong, G.Y., Gnecco, C., Pinsky, C.M., Whitmore, W.F., Fair, W.R., Oettgen, H.F. J. Clin. Oncol. (1987) [Pubmed]
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  6. Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Adams, B.D., Claffey, K.P., White, B.A. Endocrinology (2009) [Pubmed]
  7. Determinants of plasma coenzyme Q10 in humans. Kaikkonen, J., Nyyssönen, K., Tuomainen, T.P., Ristonmaa, U., Salonen, J.T. FEBS Lett. (1999) [Pubmed]
  8. Coenzyme Q10 in health and disease. Overvad, K., Diamant, B., Holm, L., Holmer, G., Mortensen, S.A., Stender, S. European journal of clinical nutrition. (1999) [Pubmed]
  9. Effect of Diamphidia toxin, a Bushman arrow poison, on ionic permeability in nucleated cells. Jacobsen, T.F., Sand, O., Bjøro, T., Karlsen, H.E., Iversen, J.G. Toxicon (1990) [Pubmed]
  10. Caudate volume as an outcome measure in clinical trials for Huntington's disease: a pilot study. Aylward, E.H., Rosenblatt, A., Field, K., Yallapragada, V., Kieburtz, K., McDermott, M., Raymond, L.A., Almqvist, E.W., Hayden, M., Ross, C.A. Brain Res. Bull. (2003) [Pubmed]
  11. Statins, cholesterol, Co-enzyme Q10, and Parkinson's disease. Lieberman, A., Lyons, K., Levine, J., Myerburg, R. Parkinsonism Relat. Disord. (2005) [Pubmed]
  12. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Maniataki, E., Mourelatos, Z. Genes Dev. (2005) [Pubmed]
  13. Slicer function of Drosophila Argonautes and its involvement in RISC formation. Miyoshi, K., Tsukumo, H., Nagami, T., Siomi, H., Siomi, M.C. Genes Dev. (2005) [Pubmed]
  14. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., Tuschl, T. Mol. Cell (2004) [Pubmed]
  15. Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis. Toossi, Z., Kleinhenz, M.E., Ellner, J.J. J. Exp. Med. (1986) [Pubmed]
  16. Description of Gluconacetobacter sacchari sp. nov., a new species of acetic acid bacterium isolated from the leaf sheath of sugar cane and from the pink sugar-cane mealy bug. Franke, I.H., Fegan, M., Hayward, C., Leonard, G., Stackebrandt, E., Sly, L.I. Int. J. Syst. Bacteriol. (1999) [Pubmed]
  17. Clinical laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Steele, P.E., Tang, P.H., DeGrauw, A.J., Miles, M.V. Am. J. Clin. Pathol. (2004) [Pubmed]
  18. Vaccinations with T-helper type 1 directing adjuvants have different suppressive effects on the development of allergen-induced T-helper type 2 responses. Trujillo-Vargas, C.M., Mayer, K.D., Bickert, T., Palmetshofer, A., Grunewald, S., Ramirez-Pineda, J.R., Polte, T., Hansen, G., Wohlleben, G., Erb, K.J. Clin. Exp. Allergy (2005) [Pubmed]
  19. Hypoxia, temperature, and pH/CO2 effects on respiratory discharge from a turtle brain stem preparation. Johnson, S.M., Johnson, R.A., Mitchell, G.S. J. Appl. Physiol. (1998) [Pubmed]
  20. Measurement of antigen-dependent interleukin-4 production by human peripheral blood mononuclear cells. Introduction of an amplification step using ionomycin and phorbol myristate acetate. Kurtzhals, J.A., Hansen, M.B., Hey, A.S., Poulsen, L.K. J. Immunol. Methods (1992) [Pubmed]
  21. Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells. Schmitter, D., Filkowski, J., Sewer, A., Pillai, R.S., Oakeley, E.J., Zavolan, M., Svoboda, P., Filipowicz, W. Nucleic Acids Res. (2006) [Pubmed]
  22. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Sen, G.L., Blau, H.M. Nat. Cell Biol. (2005) [Pubmed]
  23. Detection of the argonaute protein Ago2 and microRNAs in the RNA induced silencing complex (RISC) using a monoclonal antibody. Ikeda, K., Satoh, M., Pauley, K.M., Fritzler, M.J., Reeves, W.H., Chan, E.K. J. Immunol. Methods (2006) [Pubmed]
  24. ago1 and dcr1, two core components of the RNA interference pathway, functionally diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe. Carmichael, J.B., Provost, P., Ekwall, K., Hobman, T.C. Mol. Biol. Cell (2004) [Pubmed]
  25. Exploring the functions of RNA interference pathway proteins: some functions are more RISCy than others? Jaronczyk, K., Carmichael, J.B., Hobman, T.C. Biochem. J. (2005) [Pubmed]
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  30. A cysteine-specific lysosomal transport system provides a major route for the delivery of thiol to human fibroblast lysosomes: possible role in supporting lysosomal proteolysis. Pisoni, R.L., Acker, T.L., Lisowski, K.M., Lemons, R.M., Thoene, J.G. J. Cell Biol. (1990) [Pubmed]
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  33. Two RAREs and an overlapping CRE are involved in the hepatic transcriptional regulation of the Q10 MHC class I gene. David-Watine, B., Yaniv, M. Cell Death Differ. (1996) [Pubmed]
  34. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R. Nature (2005) [Pubmed]
  35. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. Tahbaz, N., Kolb, F.A., Zhang, H., Jaronczyk, K., Filipowicz, W., Hobman, T.C. EMBO Rep. (2004) [Pubmed]
  36. Identification of novel argonaute-associated proteins. Meister, G., Landthaler, M., Peters, L., Chen, P.Y., Urlaub, H., Lührmann, R., Tuschl, T. Curr. Biol. (2005) [Pubmed]
  37. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Patel, S.R., White, D.P., Malhotra, A., Stanchina, M.L., Ayas, N.T. Arch. Intern. Med. (2003) [Pubmed]
  38. SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye. Grus, F.H., Podust, V.N., Bruns, K., Lackner, K., Fu, S., Dalmasso, E.A., Wirthlin, A., Pfeiffer, N. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  39. Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle, and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard. Duncan, A.J., Heales, S.J., Mills, K., Eaton, S., Land, J.M., Hargreaves, I.P. Clin. Chem. (2005) [Pubmed]
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