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Gene Review

ELAC2  -  elaC ribonuclease Z 2

Homo sapiens

Synonyms: COXPD17, ELC2, ElaC homolog protein 2, FLJ10530, HPC2, ...
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Disease relevance of ELAC2

  • The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V.Tavtigian et al. Nat. Genet., 27:172-180, 2001) [1].
  • We cloned a human ELAC2 cDNA and expressed the ELAC2 protein in Escherichia coli [2].
  • 9-Nitrocamptothecin was given orally at 0.44, 0.67, or 1.0 mg/kg/d qd x 5d x 2 weeks repeated q 4 weeks for two cycles to female C.B-17 SCID mice bearing HT29 or ELC2 human colon xenografts [3].

High impact information on ELAC2


Chemical compound and disease context of ELAC2

  • Although the Leu217 and Thr541 variants of ELAC2 are less common in Japanese than in Caucasians, both variants confer significantly increased risk of prostate cancer in Japanese. Carriage of these variants was not associated with age at diagnosis, tumor stage, or tumor grade in these Japanese prostate cancer patients [9].
  • There is, however, little evidence for excess clustering of the T allele within the multiplex families known to be segregating this allele, and there is no evidence for linkage of prostate cancer to the HPC2/ELAC2 region of chromosome 17p11.2 in these families [10].

Biological context of ELAC2

  • Nonetheless, the discovery of the first prostate cancer susceptibility gene characterized by positional cloning, ELAC2 was achieved taking advantage of the Utah Family Resource. Moreover, common missense mutations in the ELAC2 gene were found to be significantly associated with an increased risk of diagnosis of prostate cancer in some studies [11].
  • Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2 [12].
  • Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk [13].
  • Seven ELAC2 variants which contain one to three amino acid substitutions showed efficient 3'-tRNase activities, while one truncated variant, which lacked a C-terminal half region, had no activity [2].
  • In the human genome exists a gene, ELAC1, which seems to correspond to the C-terminal half of 3' tRNase from ELAC2 [2].

Anatomical context of ELAC2

  • However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC [8].
  • The highest levels of expression of the ELAC2 form are observed in the testis while the lowest levels are seen in the prostate and in the muscle [14].

Regulatory relationships of ELAC2

  • RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented [13].
  • Small interfering siRNA-mediated knock-down of ELAC2 in prostate cells suppressed TGF-beta-induced growth arrest [15].

Other interactions of ELAC2

  • CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease [13].
  • Overexpression of ELAC2 in tumor cells causes a delay in G2-M progression characterized by accumulation of cyclin B levels [16].
  • In this study, we found that the candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-beta/Smad-induced transcriptional responses [15].
  • Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-beta/Smad signaling mediated growth arrest.Oncogene (2006) 25, 5591-5600. doi:10.1038/sj.onc.1209571; published online 24 April 2006 [15].

Analytical, diagnostic and therapeutic context of ELAC2


  1. ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer. Rökman, A., Ikonen, T., Mononen, N., Autio, V., Matikainen, M.P., Koivisto, P.A., Tammela, T.L., Kallioniemi, O.P., Schleutker, J. Cancer Res. (2001) [Pubmed]
  2. A candidate prostate cancer susceptibility gene encodes tRNA 3' processing endoribonuclease. Takaku, H., Minagawa, A., Takagi, M., Nashimoto, M. Nucleic Acids Res. (2003) [Pubmed]
  3. Relationship between plasma exposure of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite and antitumor response in mice bearing human colon carcinoma xenografts. Zamboni, W.C., Jung, L.L., Egorin, M.J., Hamburger, D.R., Joseph, E., Jin, R., Strychor, S., Ramanathan, R.K., Eiseman, J.L. Clin. Cancer Res. (2005) [Pubmed]
  4. Meta-analysis of associations of the Ser217Leu and Ala541Thr variants in ELAC2 (HPC2) and prostate cancer. Camp, N.J., Tavtigian, S.V. Am. J. Hum. Genet. (2002) [Pubmed]
  5. Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer. Xu, J., Zheng, S.L., Carpten, J.D., Nupponen, N.N., Robbins, C.M., Mestre, J., Moses, T.Y., Faith, D.A., Kelly, B.D., Isaacs, S.D., Wiley, K.E., Ewing, C.M., Bujnovszky, P., Chang , B., Bailey-Wilson, J., Bleecker, E.R., Walsh, P.C., Trent, J.M., Meyers, D.A., Isaacs, W.B. Am. J. Hum. Genet. (2001) [Pubmed]
  6. Association of HPC2/ELAC2 genotypes and prostate cancer. Rebbeck, T.R., Walker, A.H., Zeigler-Johnson, C., Weisburg, S., Martin, A.M., Nathanson, K.L., Wein, A.J., Malkowicz, S.B. Am. J. Hum. Genet. (2000) [Pubmed]
  7. Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins. Sewalt, R.G., Lachner, M., Vargas, M., Hamer, K.M., den Blaauwen, J.L., Hendrix, T., Melcher, M., Schweizer, D., Jenuwein, T., Otte, A.P. Mol. Cell. Biol. (2002) [Pubmed]
  8. Role of HPC2/ELAC2 in hereditary prostate cancer. Wang, L., McDonnell, S.K., Elkins, D.A., Slager, S.L., Christensen, E., Marks, A.F., Cunningham, J.M., Peterson, B.J., Jacobsen, S.J., Cerhan, J.R., Blute, M.L., Schaid, D.J., Thibodeau, S.N. Cancer Res. (2001) [Pubmed]
  9. Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a Japanese case-control series. Fujiwara, H., Emi, M., Nagai, H., Nishimura, T., Konishi, N., Kubota, Y., Ichikawa, T., Takahashi, S., Shuin, T., Habuchi, T., Ogawa, O., Inoue, K., Skolnick, M.H., Swensen, J., Camp, N.J., Tavtigian, S.V. J. Hum. Genet. (2002) [Pubmed]
  10. Polymorphisms in the prostate cancer susceptibility gene HPC2/ELAC2 in multiplex families and healthy controls. Suarez, B.K., Gerhard, D.S., Lin, J., Haberer, B., Nguyen, L., Kesterson, N.K., Catalona, W.J. Cancer Res. (2001) [Pubmed]
  11. Perspective: prostate cancer susceptibility genes. Simard, J., Dumont, M., Soucy, P., Labrie, F. Endocrinology (2002) [Pubmed]
  12. Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1. Lange, E.M., Gillanders, E.M., Davis, C.C., Brown, W.M., Campbell, J.K., Jones, M., Gildea, D., Riedesel, E., Albertus, J., Freas-Lutz, D., Markey, C., Giri, V., Dimmer, J.B., Montie, J.E., Trent, J.M., Cooney, K.A. Prostate (2003) [Pubmed]
  13. Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma. Noonan-Wheeler, F.C., Wu, W., Roehl, K.A., Klim, A., Haugen, J., Suarez, B.K., Kibel, A.S. Prostate (2006) [Pubmed]
  14. Structure of primate and rodent orthologs of the prostate cancer susceptibility gene ELAC2. Dumont, M., Frank, D., Moisan, A.M., Tranchant, M., Soucy, P., Breton, R., Labrie, F., Tavtigian, S.V., Simard, J. Biochim. Biophys. Acta (2004) [Pubmed]
  15. ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cells. Noda, D., Itoh, S., Watanabe, Y., Inamitsu, M., Dennler, S., Itoh, F., Koike, S., Danielpour, D., Ten Dijke, P., Kato, M. Oncogene (2006) [Pubmed]
  16. The product of the candidate prostate cancer susceptibility gene ELAC2 interacts with the gamma-tubulin complex. Korver, W., Guevara, C., Chen, Y., Neuteboom, S., Bookstein, R., Tavtigian, S., Lees, E. Int. J. Cancer (2003) [Pubmed]
  17. Association of HPC2/ELAC2 polymorphisms with risk of prostate cancer in a population-based study. Stanford, J.L., Sabacan, L.P., Noonan, E.A., Iwasaki, L., Shu, J., Feng, Z., Ostrander, E.A. Cancer Epidemiol. Biomarkers Prev. (2003) [Pubmed]
  18. Loss of heterozygosity of the putative prostate cancer susceptibility gene HPC2/ELAC2 is uncommon in sporadic and familial prostate cancer. Wu, Y.Q., Chen, H., Rubin, M.A., Wojno, K.J., Cooney, K.A. Cancer Res. (2001) [Pubmed]
  19. Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men. Takahashi, H., Lu, W., Watanabe, M., Katoh, T., Furusato, M., Tsukino, H., Nakao, H., Sudo, A., Suzuki, H., Akakura, K., Ikemoto, I., Asano, K., Ito, T., Wakui, S., Muto, T., Hano, H. Int. J. Cancer (2003) [Pubmed]
  20. A panel of monoclonal antibodies against human polycomb group proteins. Hamer, K.M., Sewalt, R.G., den Blaauwen, J.L., Hendrix, T., Satijn, D.P., Otte, A.P. Hybrid. Hybridomics (2002) [Pubmed]
  21. The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2. Qin, H., Du, D., Zhu, Y., Li, J., Feng, L., Liang, Y., Han, H. FEBS Lett. (2005) [Pubmed]
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