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CBX8  -  chromobox homolog 8

Homo sapiens

Synonyms: Chromobox protein homolog 8, HPC3, PC3, Pc3, Polycomb 3 homolog, ...
 
 
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Disease relevance of CBX8

  • With the aid of monoclonal antibody (mAb) 2625, raised against the lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we isolated mutant 811 from the virulent wild-type strain RC1 [1].
  • Inhibition of 5-lipoxygenase by MK886 completely blocks 5-HETE production and induces massive apoptosis in both hormone-responsive (LNCaP) and -nonresponsive (PC3) human prostate cancer cells [2].
  • This protein strongly inhibited DNA synthesis in two metastatic androgen-independent human prostatic carcinoma cell lines (PC3 and DU145) and the Dunning R3327G rat prostatic adenocarcinoma [3].
  • We have probed for the presence of interleukin 6 (IL6) receptors in prostatic carcinoma cell lines (LNCaP, DU 145, and PC3) by examining their sensitivity to the cytotoxic effects of a chimeric toxin composed of IL6 and Pseudomonas exotoxin (PE) [4].
  • Three double negative (BoCD4-, BoCD8-) bovine T cell lines, BTL-PC3, BLT2, and Pr2181, which have been established from bovine lymphosarcomas, were examined for expression and molecular function of bovine c-myb genes [5].
 

High impact information on CBX8

  • The rodent Pc3/Tis21 gene was initially described as an immediate early gene induced by tumour promoters and growth factors in PC12 and Swiss 3T3 cells [6].
  • Here, we demonstrate that the chromodomain-containing protein, CBX8, which is part of one of the PRC1 complexes, regulates proliferation of diploid human and mouse fibroblasts through direct binding to the INK4A-ARF locus [7].
  • Gene expression and location analysis demonstrate that besides the INK4A-ARF locus, CBX8 also regulates a number of other genes important for cell growth and survival [7].
  • Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus [7].
  • Seven of the 10 amino acid substitutions in PC3 are found in other natural subtilisins [8].
 

Chemical compound and disease context of CBX8

 

Biological context of CBX8

  • The PCA of the 1H NMR spectra of the aqueous fractions allowed a clear discrimination between antler samples according to their origins by the first three principal components (PC1, PC2, and PC3), which cumulatively accounted for 93.5% of the variation in all variables [13].
  • Sequential rounds of mutagenesis and screening have yielded a variant (PC3) that hydrolyzes a peptide substrate 256 times more efficiently than wild-type subtilisin in 60% dimethylformamide [8].
  • The purpose of the present study was to investigate the role of transforming growth factor alpha (TGF-alpha) and its receptor, the epidermal growth factor (EGF) receptor, in the regulation of PC3 cell proliferation [14].
  • PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures [15].
  • In addition, genomic instability in the prostate cell lines including DU145, PC3, LNCaP, p67SV40T, M2182, and M12 was detected by a microsatellite mutation assay [16].
 

Anatomical context of CBX8

 

Associations of CBX8 with chemical compounds

  • Radioligand-binding assays revealed the presence of high affinity sites of estrogen binding in the nuclear compartment of PC3 cells [9].
  • To gain more insight into structure-activity relationships of suramin, we investigated the antiproliferative action of suramin and 19 suramin analogues in vitro using 5 different human cell lines (HT29, MCF7, SW13, PC3, and T47D) [21].
  • The RC0.1 and RC1 cells have high cross-resistance to CPT derivatives including SN-38 and topotecan, but are not cross-resistant to the non-top1 inhibitors etoposide, doxorubicin, and vincristine [22].
  • The PC3 growth factor did not bind to heparin and was resistant to acid as well as the reducing agent, dithiothreitol [15].
  • The CPT-resistant cell lines and corresponding mutations were: human prostate carcinoma cells DU-145/RC1 (mutation R364H), Chinese hamster fibroblasts DC3F/C10 (mutation G503S), and human leukemia CEM/C2 cells (N722S) [23].
 

Physical interactions of CBX8

  • An internal region of hPc3 was responsible for binding to ENL [17].
  • Finally, hPc3 binds to the C-terminus of AF9, another common MLL fusion partner [17].
 

Other interactions of CBX8

  • This interaction is dependent upon the HPC3 C-box but, only partially on the RING finger of RING1 [24].
  • The ENL-hPc3 interaction was verified by mutual co-precipitation of the proteins from cell extracts [17].
  • RESULTS: Compared with parental HPC-3, HPC-3H4 displayed higher telomerase activity, which was associated with a scattered phenotype and enhanced migration activity [25].
 

Analytical, diagnostic and therapeutic context of CBX8

References

  1. Phase-variable expression of lipopolysaccharide contributes to the virulence of legionella pneumophila. Lüneberg, E., Zähringer, U., Knirel, Y.A., Steinmann, D., Hartmann, M., Steinmetz, I., Rohde, M., Köhl, J., Frosch, M. J. Exp. Med. (1998) [Pubmed]
  2. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Ghosh, J., Myers, C.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Isolation of a prostate carcinoma cell proliferation-inhibiting factor from human seminal plasma and its similarity to transforming growth factor beta. Lokeshwar, B.L., Block, N.L. Cancer Res. (1992) [Pubmed]
  4. Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. Siegall, C.B., Schwab, G., Nordan, R.P., FitzGerald, D.J., Pastan, I. Cancer Res. (1990) [Pubmed]
  5. A spontaneous internal deletion of the c-myb protooncogene enhances transcriptional activation in bovine T lymphoma cells. Ishiguro, N., Ohzono, T., Shinagawa, T., Horiuchi, M., Shinagawa, M. J. Biol. Chem. (1994) [Pubmed]
  6. Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Rouault, J.P., Falette, N., Guéhenneux, F., Guillot, C., Rimokh, R., Wang, Q., Berthet, C., Moyret-Lalle, C., Savatier, P., Pain, B., Shaw, P., Berger, R., Samarut, J., Magaud, J.P., Ozturk, M., Samarut, C., Puisieux, A. Nat. Genet. (1996) [Pubmed]
  7. Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. Dietrich, N., Bracken, A.P., Trinh, E., Schjerling, C.K., Koseki, H., Rappsilber, J., Helin, K., Hansen, K.H. EMBO J. (2007) [Pubmed]
  8. Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. Chen, K., Arnold, F.H. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Estradiol inhibits growth of hormone-nonresponsive PC3 human prostate cancer cells. Carruba, G., Pfeffer, U., Fecarotta, E., Coviello, D.A., D'Amato, E., Lo Castro, M., Vidali, G., Castagnetta, L. Cancer Res. (1994) [Pubmed]
  10. Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1. Degeorges, A., Wang, F., Frierson, H.F., Seth, A., Chung, L.W., Sikes, R.A. Cancer Res. (1999) [Pubmed]
  11. Melatonin receptors in PC3 human prostate tumor cells. Gilad, E., Laufer, M., Matzkin, H., Zisapel, N. J. Pineal Res. (1999) [Pubmed]
  12. Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin. Smith, J.A., Madden, T., Vijjeswarapu, M., Newman, R.A. Biochem. Pharmacol. (2001) [Pubmed]
  13. Metabolomic differentiation of deer antlers of various origins by 1H NMR spectrometry and principal components analysis. Choi, H.K., Kim, K.H., Kim, K.H., Kim, Y.S., Lee, M.W., Whang, W.K. Journal of pharmaceutical and biomedical analysis. (2006) [Pubmed]
  14. Autonomous growth of androgen-independent human prostatic carcinoma cells: role of transforming growth factor alpha. Hofer, D.R., Sherwood, E.R., Bromberg, W.D., Mendelsohn, J., Lee, C., Kozlowski, J.M. Cancer Res. (1991) [Pubmed]
  15. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells. Perkel, V.S., Mohan, S., Herring, S.J., Baylink, D.J., Linkhart, T.A. Cancer Res. (1990) [Pubmed]
  16. Defects of DNA mismatch repair in human prostate cancer. Chen, Y., Wang, J., Fraig, M.M., Metcalf, J., Turner, W.R., Bissada, N.K., Watson, D.K., Schweinfest, C.W. Cancer Res. (2001) [Pubmed]
  17. The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3. García-Cuéllar, M.P., Zilles, O., Schreiner, S.A., Birke, M., Winkler, T.H., Slany, R.K. Oncogene (2001) [Pubmed]
  18. Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II. Kretzschmar, M., Meisterernst, M., Roeder, R.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  19. Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow apoptosis and intracellular drug retention. Au, J.L., Li, D., Gan, Y., Gao, X., Johnson, A.L., Johnston, J., Millenbaugh, N.J., Jang, S.H., Kuh, H.J., Chen, C.T., Wientjes, M.G. Cancer Res. (1998) [Pubmed]
  20. Epidermal growth factor receptor monoclonal antibody inhibits constitutive receptor phosphorylation, reduces autonomous growth, and sensitizes androgen-independent prostatic carcinoma cells to tumor necrosis factor alpha. Fong, C.J., Sherwood, E.R., Mendelsohn, J., Lee, C., Kozlowski, J.M. Cancer Res. (1992) [Pubmed]
  21. Antiproliferative and angiostatic activity of suramin analogues. Firsching, A., Nickel, P., Mora, P., Allolio, B. Cancer Res. (1995) [Pubmed]
  22. Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line. Urasaki, Y., Laco, G.S., Pourquier, P., Takebayashi, Y., Kohlhagen, G., Gioffre, C., Zhang, H., Chatterjee, D., Pantazis, P., Pommier, Y. Cancer Res. (2001) [Pubmed]
  23. Use of camptothecin-resistant mammalian cell lines to evaluate the role of topoisomerase I in the antiproliferative activity of the indolocarbazole, NB-506, and its topoisomerase I binding site. Urasaki, Y., Laco, G., Takebayashi, Y., Bailly, C., Kohlhagen, G., Pommier, Y. Cancer Res. (2001) [Pubmed]
  24. HPC3 is a new human polycomb orthologue that interacts and associates with RING1 and Bmi1 and has transcriptional repression properties. Bárdos, J.I., Saurin, A.J., Tissot, C., Duprez, E., Freemont, P.S. J. Biol. Chem. (2000) [Pubmed]
  25. Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion. Sato, N., Maehara, N., Mizumoto, K., Nagai, E., Yasoshima, T., Hirata, K., Tanaka, M. Cancer (2001) [Pubmed]
  26. In vitro expression of endothelin-1 (ET-1) and the ETA and ETB ET receptors by the prostatic epithelium and stroma. Grant, E.S., Brown, T., Roach, A., Williams, B.C., Habib, F.K. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
 
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