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Gene Review

NOL3  -  nucleolar protein 3 (apoptosis repressor...

Homo sapiens

Synonyms: ARC, Apoptosis repressor with CARD, CARD2, FCM, MYP, ...
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Disease relevance of NOL3

  • Loss of expression of death-inducing signaling complex (DISC) components in lung cancer cell lines and the influence of MYC amplification [1].
  • BACKGROUND: Deregulated expression of oncogenes such as MYC and PAX3-FKHR often occurs in rhabdomyosarcomas [2].
  • We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells [3].
  • Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene [4].
  • These results suggest that the type I receptor for TGF-beta in human gastric carcinoma cells may be mainly linked with the growth inhibition of TGF-beta by a decrease in retinoblastoma protein phosphorylation by p34cdc-2 without suppression of MYC expression [5].

Psychiatry related information on NOL3

  • The present study evaluated the effect of three newly synthesized peptidergic and one brain-penetrating heterocyclic NOP receptor agonists on alcohol drinking in the two bottle choice paradigm [6].
  • The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats [7].

High impact information on NOL3

  • Four of the MYC/COOH-terminal nebulin fragments were incorporated exclusively into periodic approximately 0.1-micrometer Z-bands [8].
  • To learn how nebulin functions in the assembly and maintenance of I-Z-I bands, MYC- and GFP- tagged nebulin fragments were expressed in primary cultured skeletal myotubes [8].
  • No effect on gene copy number or tumorigenicity was observed for a closely related cell line containing the same number of chromosomally amplified MYC genes [9].
  • The decreases in MYC copy number in a human tumor cell line correlated with a dramatic reduction in cloning efficiency in soft agar and tumorigenicity in nude mice [9].
  • When tumors relapsed, they no longer required the overexpression of MYC but instead acquired novel chromosomal translocations [10].

Chemical compound and disease context of NOL3


Biological context of NOL3

  • Sequencing of the NOP gene demonstrated that both cDNAs are generated by alternative 5' splice site usage from a single gene that consists of four exons, spans at least 1800 nucleotides, and is located on chromosome 16q21-q23 [13].
  • Alternative splicing determines the intracellular localization of the novel nuclear protein Nop30 and its interaction with the splicing factor SRp30c [13].
  • Overexpression of Nop30 changes alternative exon usage in preprotachykinin and SRp20 reporter genes, suggesting that Nop30 influences alternative splice site selection in vivo [13].
  • MYC family members are frequently amplified (MYC+ve) in SCLC, and MYC is a potent inducer of apoptosis [1].
  • MYC can enhance cell proliferation and apoptosis under specific conditions, whereas PAX3-FKHR has only been described as anti-apoptotic [2].

Anatomical context of NOL3

  • The carboxyl terminus of Nop30 is rich in serines and arginines and has been found to target the protein into the nucleus, whereas its isoform is characterized by proline/glutamic acid dipeptides in its carboxyl terminus and is predominantly found in the cytosol [13].
  • We found that MYC induces DNA double-strand breaks (DSBs) independent of ROS production in murine lymphocytes in vivo as well as in normal human foreskin fibroblasts (NHFs) in vitro in normal (10%) serum, as measured by gammaH2AX staining [14].
  • Because liver regeneration is an essential process for achieving liver homeostasis, therapies directed at reducing MYC expression in hepatocellular carcinoma are fraught with the theoretical possibility of injuring adjacent noncancerous liver cells, thereby restricting the liver's normal regenerative response to injury [15].
  • Subcellular distribution studies showed that MYC epitope-tagged SLAP localized to regions of juxtaposition between neighboring cell membranes although an intracellular pool of the protein was also present in cells undergoing apparent cleavage [16].
  • MYC is an important oncogene in hematopoietic neoplasms in humans, yet the mechanism by which MYC induces the malignant transformation of blood cells has remained elusive [17].

Associations of NOL3 with chemical compounds

  • Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP) [18].
  • BACKGROUND: Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats [19].
  • Nociceptin analogues in which Ala residues are substituted with aminoisobutyric acid (Aib) show a substantial increment of activity in their interaction with the NOP receptor [20].
  • Estrogen treatment increased NOP mRNA expression in anteroventral periventricular nucleus (AVPV), median preoptic nucleus, and VMH [21].
  • Subsequent progesterone treatment did not alter estrogen-induced expression of NOP mRNA in VMH or median preoptic nucleus but reduced expression in the AVPV [21].

Other interactions of NOL3

  • Our major conclusions are: (a) The death receptor pathway is differently inactivated at multiple levels in lung cancer cell lines; and (b) MYC amplification in SCLC is associated with inactivation of most components of the DISC complex, with resistance to TRAIL and with expression of c-FLIP [1].

Analytical, diagnostic and therapeutic context of NOL3


  1. Loss of expression of death-inducing signaling complex (DISC) components in lung cancer cell lines and the influence of MYC amplification. Shivapurkar, N., Reddy, J., Matta, H., Sathyanarayana, U.G., Huang, C.X., Toyooka, S., Minna, J.D., Chaudhary, P.M., Gazdar, A.F. Oncogene (2002) [Pubmed]
  2. Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma. Taylor, A.C., Schuster, K., McKenzie, P.P., Harris, L.C. Mol. Cancer (2006) [Pubmed]
  3. Spatial proximity of translocation-prone gene loci in human lymphomas. Roix, J.J., McQueen, P.G., Munson, P.J., Parada, L.A., Misteli, T. Nat. Genet. (2003) [Pubmed]
  4. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node-Negative and Lymph Node-Positive Colon Carcinomas. Grade, M., H??rmann, P., Becker, S., Hummon, A.B., Wangsa, D., Varma, S., Simon, R., Liersch, T., Becker, H., Difilippantonio, M.J., Ghadimi, B.M., Ried, T. Cancer Res. (2007) [Pubmed]
  5. Growth inhibition of transforming growth factor beta on human gastric carcinoma cells: receptor and postreceptor signaling. Ito, M., Yasui, W., Kyo, E., Yokozaki, H., Nakayama, H., Ito, H., Tahara, E. Cancer Res. (1992) [Pubmed]
  6. Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats. Economidou, D., Fedeli, A., Fardon, R.M., Weiss, F., Massi, M., Ciccocioppo, R. Peptides (2006) [Pubmed]
  7. The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats. Ciccocioppo, R., Economidou, D., Fedeli, A., Massi, M. Physiol. Behav. (2003) [Pubmed]
  8. Distinct families of Z-line targeting modules in the COOH-terminal region of nebulin. Ojima, K., Lin, Z.X., Bang, M., Holtzer, S., Matsuda, R., Labeit, S., Sweeney, H.L., Holtzer, H. J. Cell Biol. (2000) [Pubmed]
  9. Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity. Von Hoff, D.D., McGill, J.R., Forseth, B.J., Davidson, K.K., Bradley, T.P., Van Devanter, D.R., Wahl, G.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  10. Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations. Karlsson, A., Giuriato, S., Tang, F., Fung-Weier, J., Levan, G., Felsher, D.W. Blood (2003) [Pubmed]
  11. Resistant multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP-regime). Hippe, E., Clausen, N.A., Gimsing, P., Haedersdal, C. Eur. J. Haematol. (1987) [Pubmed]
  12. Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Nordic Myeloma Study Group (NMSG). Keldsen, N., Bjerrum, O.W., Dahl, I.M., Drivsholm, A., Ellegaard, J., Gadeberg, O., Gimsing, P., Grønvold, T., Hansen, M.M., Hippe, E. Eur. J. Haematol. (1993) [Pubmed]
  13. Alternative splicing determines the intracellular localization of the novel nuclear protein Nop30 and its interaction with the splicing factor SRp30c. Stoss, O., Schwaiger, F.W., Cooper, T.A., Stamm, S. J. Biol. Chem. (1999) [Pubmed]
  14. MYC can induce DNA breaks in vivo and in vitro independent of reactive oxygen species. Ray, S., Atkuri, K.R., Deb-Basu, D., Adler, A.S., Chang, H.Y., Herzenberg, L.A., Felsher, D.W. Cancer Res. (2006) [Pubmed]
  15. Conditional deletion of c-myc does not impair liver regeneration. Li, F., Xiang, Y., Potter, J., Dinavahi, R., Dang, C.V., Lee, L.A. Cancer Res. (2006) [Pubmed]
  16. Molecular cloning, expression, and chromosomal assignment of sarcolemmal-associated proteins. A family of acidic amphipathic alpha-helical proteins associated with the membrane. Wigle, J.T., Demchyshyn, L., Pratt, M.A., Staines, W.A., Salih, M., Tuana, B.S. J. Biol. Chem. (1997) [Pubmed]
  17. Uncovering MYC's full oncogenic potential in the hematopoietic system. Janz, S. Oncogene (2005) [Pubmed]
  18. Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma. Tsimberidou, A.M., McLaughlin, P., Younes, A., Rodriguez, M.A., Hagemeister, F.B., Sarris, A., Romaguera, J., Hess, M., Smith, T.L., Yang, Y., Ayala, A., Preti, A., Lee, M.S., Cabanillas, F. Blood (2002) [Pubmed]
  19. Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System. Ciccocioppo, R., Economidou, D., Rimondini, R., Sommer, W., Massi, M., Heilig, M. Biol. Psychiatry (2007) [Pubmed]
  20. The interaction of highly helical structural mutants with the NOP receptor discloses the role of the address domain of nociceptin/orphanin FQ. Tancredi, T., Carrà, G., Guerrini, R., Arduin, M., Calò, G., Regoli, D., Salvadori, S., Temussi, P.A. Chemistry (Weinheim an der Bergstrasse, Germany) (2005) [Pubmed]
  21. Site-specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system. Sinchak, K., Romeo, H.E., Micevych, P.E. J. Comp. Neurol. (2006) [Pubmed]
  22. Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies. Storlazzi, C.T., Fioretos, T., Paulsson, K., Strömbeck, B., Lassen, C., Ahlgren, T., Juliusson, G., Mitelman, F., Rocchi, M., Johansson, B. Hum. Mol. Genet. (2004) [Pubmed]
  23. MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors. Peter, M., Rosty, C., Couturier, J., Radvanyi, F., Teshima, H., Sastre-Garau, X. Oncogene (2006) [Pubmed]
  24. Application of a modified real-time PCR technique for relative gene copy number quantification to the determination of the relationship between NKX3.1 loss and MYC gain in prostate cancer. Kindich, R., Florl, A.R., Jung, V., Engers, R., Müller, M., Schulz, W.A., Wullich, B. Clin. Chem. (2005) [Pubmed]
  25. Long-range chromatin analysis of the human MYC locus by pulsed-field gel electrophoresis. Mautner, J., Bornkamm, G.W., Polack, A. Genes Chromosomes Cancer (1996) [Pubmed]
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