oncogene proteins v rel


Summary: Transforming proteins coded by rel oncogenes. The v-rel protein competes with rel-related proteins and probably transforms cells by acting as a dominant negative version of c-rel. This results in the induction of a broad range of leukemias and lymphomas.

Top Publications

  1. Fujii M, Minamino T, Nomura M, Miyamoto K, Tanaka J, Seiki M. v-Rel activates the proto-oncogene c-Jun promoter: a correlation with its transforming activity. Leukemia. 1997;11 Suppl 3:402-4 pubmed
    ..Since c-Jun plays pivotal roles on cell proliferation in various types of cells, the activation of c-jun expression by v-Rel may be an essential step for the oncogenic transformation caused by v-Rel. ..
  2. Tam W, Lee L, Davis L, Sen R. Cytoplasmic sequestration of rel proteins by IkappaBalpha requires CRM1-dependent nuclear export. Mol Cell Biol. 2000;20:2269-84 pubmed
    ..We propose that the nucleus is the major site of p65-IkappaBalpha association, from where these complexes must be exported in order to create the cytoplasmic pool. ..
  3. Carrasco D, Rizzo C, Dorfman K, Bravo R. The v-rel oncogene promotes malignant T-cell leukemia/lymphoma in transgenic mice. EMBO J. 1996;15:3640-50 pubmed
    ..These v-Rel mice should aid in the study of lymphoma development, T-cell development and NF-kappa B regulation. ..
  4. Majid S, Liss A, You M, Bose H. The suppression of SH3BGRL is important for v-Rel-mediated transformation. Oncogene. 2006;25:756-68 pubmed
    ..This study provides the first example of a gene that is downregulated in v-Rel-expressing cells that also plays a role in v-Rel transformation. ..
  5. Mathas S, Johrens K, Joos S, Lietz A, Hummel F, Janz M, et al. Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas. Blood. 2005;106:4287-93 pubmed
    ..Together, these data suggest that elevated Bcl-3 expression has an important function in cHL and peripheral T-NHL, in particular ALCL. ..
  6. Hrdlickova R, Nehyba J, Humphries E. v-rel induces expression of three avian immunoregulatory surface receptors more efficiently than c-rel. J Virol. 1994;68:308-19 pubmed
  7. Gilmore T. Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel. Oncogene. 1999;18:6925-37 pubmed
    ..This review will discuss biological and molecular activities of v-Rel, with particular attention to how these activities relate to structure - function aspects of the Rel/NF-kappaB transcription factors. ..
  8. Kralova J, Liss A, Bargmann W, Bose H. AP-1 factors play an important role in transformation induced by the v-rel oncogene. Mol Cell Biol. 1998;18:2997-3009 pubmed
    ..This is the first report showing that v-Rel might execute its oncogenic potential through modulating the activity of early response genes. ..
  9. Morrison L, Boehmelt G, Beug H, Enrietto P. Expression of v-rel in a replication competent virus: transformation and biochemical characterization. Oncogene. 1991;6:1657-66 pubmed
    ..We also demonstrate that the RCAS-rel-transformed hematopoietic cells exhibited a distinct differentiation phenotype. ..

More Information


  1. Hrdlickova R, Nehyba J, Bose H. Interferon regulatory factor 4 contributes to transformation of v-Rel-expressing fibroblasts. Mol Cell Biol. 2001;21:6369-86 pubmed
    ..These results suggest that induction of IRF-4 expression by v-Rel likely facilitates transformation of fibroblasts by decreasing the induction of this antiproliferative pathway. ..
  2. Liss A, Bose H. Mutational analysis of the v-Rel dimerization interface reveals a critical role for v-Rel homodimers in transformation. J Virol. 2002;76:4928-39 pubmed
    ..Viruses expressing these proteins transformed cells at levels comparable to or slightly less than v-Rel, suggesting that a threshold level of DNA binding by v-Rel homodimers is required for transformation...
  3. Gilmore T. The Re1/NF-kappa B/I kappa B signal transduction pathway and cancer. Cancer Treat Res. 2003;115:241-65 pubmed
  4. Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed
  5. Gilmore T. Role of rel family genes in normal and malignant lymphoid cell growth. Cancer Surv. 1992;15:69-87 pubmed
    ..In addition, rel proteins are likely to be involved in T cell diseases caused by the human retroviruses HTLV-I and HIV-1. Therefore, rel proteins could serve as targets for anti-viral or anti-cancer therapies. ..
  6. Diehl J, McKinsey T, Hannink M. Differential pp40I kappa B-beta inhibition of DNA binding by rel proteins. Mol Cell Biol. 1993;13:1769-78 pubmed
    ..These results demonstrate the presence of an interaction between internal and C-terminal regions of the c-rel protein that is important for the ability of c-rel to regulate the proliferation of lymphoid cells. ..
  7. Boehmelt G, Walker A, Kabrun N, Mellitzer G, Beug H, Zenke M, et al. Hormone-regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression. EMBO J. 1992;11:4641-52 pubmed
    ..These results suggest that v-rel might exert part of its activity as an activator of rel-responsive genes. ..
  8. Gilmore T. Malignant transformation by mutant Rel proteins. Trends Genet. 1991;7:318-22 pubmed
    ..Nevertheless, there is still much to be learned about their precise mechanism of action, including the process by which the original member of this family, v-Rel, malignantly transforms cells. ..
  9. Richardson P, Gilmore T. vRel is an inactive member of the Rel family of transcriptional activating proteins. J Virol. 1991;65:3122-30 pubmed
    ..Our results suggest that vRel transforms cells by interfering with transcriptional activation by cellular Rel proteins. ..
  10. Sarkar S, Gilmore T. Transformation by the vRel oncoprotein requires sequences carboxy-terminal to the Rel homology domain. Oncogene. 1993;8:2245-52 pubmed
    ..These observations suggest that vRel induces malignant transformation by directly altering gene expression. ..
  11. Petrenko O, Ischenko I, Enrietto P. Isolation of a cDNA encoding a novel chicken chemokine homologous to mammalian macrophage inflammatory protein-1 beta. Gene. 1995;160:305-6 pubmed
    ..All conserved amino acids characteristic of the mammalian chemokine family have been evolutionarily preserved in chicken MIP-1 beta, suggesting similar protein folding patterns and functional properties. ..
  12. Moore B, Bose H. Transformation of avian lymphoid cells by reticuloendotheliosis virus. Mutat Res. 1988;195:79-90 pubmed
    ..This review discusses the molecular aspects of transformation by REV-T in the context of other oncogene-encoded proteins...
  13. Xu X, Gelinas C. The v-Rel oncoprotein complexes with new Rel- and RelA-related proteins in transformed cells. Virology. 1995;207:362-8 pubmed
  14. Ruocco M, Chen X, Ambrosino C, Dragonetti E, Liu W, Mallardo M, et al. Regulation of HIV-1 long terminal repeats by interaction of C/EBP(NF-IL6) and NF-kappaB/Rel transcription factors. J Biol Chem. 1996;271:22479-86 pubmed
    ..By using mutant forms of p50 or C/EBPbeta proteins we found that the transactivation of HIV-1 LTR by p50 middle dotC/EBPbeta complexes required the DNA-binding domain of p50 and the transcription activation domain of C/EBPbeta. ..
  15. Hrdlickova R, Nehyba J, Humphries E. In vivo evolution of c-rel oncogenic potential. J Virol. 1994;68:2371-82 pubmed
    ..Moreover, an analysis of the subcellular localization of different rel proteins revealed an inverse correlation between the size of the protein and the proportion in the nucleus of lymphoid cells. ..
  16. Marpegan L, Bekinschtein T, Freudenthal R, Rubio M, Ferreyra G, Romano A, et al. Participation of transcription factors from the Rel/NF-kappa B family in the circadian system in hamsters. Neurosci Lett. 2004;358:9-12 pubmed
    ..36+/-0.35 h). These results demonstrate the presence and activity of Rel/NF-kappaB family proteins in the hamster SCN and suggest that these proteins may be related to the entrainment and regulation of circadian rhythms. ..
  17. Kumar S, Gelinas C. I kappa B alpha-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/kappa B DNA-binding motif. Proc Natl Acad Sci U S A. 1993;90:8962-6 pubmed
  18. Xu X, Prorock C, Ishikawa H, Maldonado E, Ito Y, Gelinas C. Functional interaction of the v-Rel and c-Rel oncoproteins with the TATA-binding protein and association with transcription factor IIB. Mol Cell Biol. 1993;13:6733-41 pubmed
  19. Dushay M, Eldon E. Drosophila immune responses as models for human immunity. Am J Hum Genet. 1998;62:10-4 pubmed
  20. Leeman J, Weniger M, Barth T, Gilmore T. Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL. Oncogene. 2008;27:6770-81 pubmed publisher
  21. Maggirwar S, Harhaj E, Sun S. Regulation of the interleukin-2 CD28-responsive element by NF-ATp and various NF-kappaB/Rel transcription factors. Mol Cell Biol. 1997;17:2605-14 pubmed
    ..Together, these results suggest that activation of IL-2 gene transcription by the TCR- and CD28-mediated signals involves the interaction of CD28RE with NF-ATp and various NF-kappaB/Rel transcription factors. ..
  22. Hrdlicková R, Nehyba J, Liss A, Bose H. Mechanism of telomerase activation by v-Rel and its contribution to transformation. J Virol. 2006;80:281-95 pubmed
    ..In contrast, the ectopic expression of TERT decreased the extent of apoptosis induced by ROS. The activation of telomerase by v-Rel may, therefore, partially protect the transformed cells from apoptosis induced by ROS. ..
  23. Bearer E. Distribution of Xrel in the early Xenopus embryo: a cytoplasmic and nuclear gradient. Eur J Cell Biol. 1994;63:255-68 pubmed
    ..The presence of this putative transcription factor in the nuclei of these cells prior to mid-blastula transition suggests that Xrel-1 may be involved in programming animal cells to respond to vegetal-inducing factors. ..
  24. Romero P, Humphries E. A mutant v-rel with increased ability to transform B lymphocytes. J Virol. 1995;69:301-7 pubmed
    ..This mutation is close to the DNA-binding region, and the variant v-Rel oncoprotein shows increased kappa B-binding activity, thus confirming the relevance of this property for transformation. ..
  25. Sif S, Gilmore T. Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1. J Virol. 1994;68:7131-8 pubmed
  26. Hrdlickova R, Nehyba J, Bose H. Mutations in the DNA-binding and dimerization domains of v-Rel are responsible for altered kappa B DNA-binding complexes in transformed cells. J Virol. 1995;69:3369-80 pubmed
    ..These results suggest that two different regions of v-Rel (both located in the RH domain) influence the formation of kappa B DNA-binding complexes differently. ..
  27. Santourlidis S, Warskulat U, Florl A, Maas S, Pulte T, Fischer J, et al. Hypermethylation of the tumor necrosis factor receptor superfamily 6 (APT1, Fas, CD95/Apo-1) gene promoter at rel/nuclear factor kappaB sites in prostatic carcinoma. Mol Carcinog. 2001;32:36-43 pubmed
    ..Thus, although the TNFRSF6 gene can be inactivated efficiently by DNA methylation, hypermethylation occurs neither frequently nor extensively in human carcinomas and appears to play a limited role in downregulation of Fas expression. ..
  28. van Hogerlinden M, Auer G, Toftgard R. Inhibition of Rel/Nuclear Factor-kappaB signaling in skin results in defective DNA damage-induced cell cycle arrest and Ha-ras- and p53-independent tumor development. Oncogene. 2002;21:4969-77 pubmed
    ..These findings demonstrate an involvement of NF-kappaB signaling in the DNA damage response and cell cycle checkpoint control in the skin. ..
  29. Barkett M, Dooher J, Lemonnier L, Simmons L, Scarpati J, Wang Y, et al. Three mutations in v-Rel render it resistant to cleavage by cell-death protease caspase-3. Biochim Biophys Acta. 2001;1526:25-36 pubmed
    ..Nevertheless, to our knowledge, this is the first demonstration of mutations in caspase-3 recognition sites occurring during the evolution of an oncogenic protein. ..
  30. Fu S, Ganter B, Lipsick J. Myb proteins inhibit fibroblast transformation by v-Rel. Mol Cancer. 2006;5:54 pubmed
    ..These results imply that the myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts. ..
  31. Huang D, Chen Y, Ruetsche M, Phelps C, Ghosh G. X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2. Structure. 2001;9:669-78 pubmed
    ..Two amino acid changes in these segments may account for the differential DNA binding by v-Rel as compared to that of c-Rel. ..
  32. Gilmore T, Cormier C, Jean Jacques J, Gapuzan M. Malignant transformation of primary chicken spleen cells by human transcription factor c-Rel. Oncogene. 2001;20:7098-103 pubmed
    ..These results are the first demonstration of a lymphoid cell malignant transforming ability for mammalian Rel/NF-kappaB transcription factors, and implicate c-Rel as a molecular target for cancer therapeutics. ..
  33. Fan G, Fan Y, Gupta N, Matsuura I, Liu F, Zhou X, et al. Peptidyl-prolyl isomerase Pin1 markedly enhances the oncogenic activity of the rel proteins in the nuclear factor-kappaB family. Cancer Res. 2009;69:4589-97 pubmed publisher
    ..Together, these results show that Pin1 is an important regulator of Rel/NF-kappaB transforming activity and suggest that Pin1 may be a potential therapeutic target in Rel/NF-kappaB-dependent leukemia/lymphomas. ..
  34. Liu J, Perkins N, Schmid R, Nabel G. Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. J Virol. 1992;66:3883-7 pubmed
    ..These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA. ..
  35. White D, Gilmore T. Bcl-2 and CrmA have different effects on transformation, apoptosis and the stability of I kappa B-alpha in chicken spleen cells transformed by temperature-sensitive v-Rel oncoproteins. Oncogene. 1996;13:891-9 pubmed
    ..In summary, these results suggest that v-Rel immortalizes chicken spleen cells through a pathway that involves the Bcl-2 family of proteins, and suggest that one pathway of proteolysis of I kappa B-alpha involves an ICE-like protease. ..
  36. Grumont R, Gerondakis S. Structure of a mammalian c-rel protein deduced from the nucleotide sequence of murine cDNA clones. Oncogene Res. 1989;4:1-8 pubmed
    ..This suggests that the conserved domain of the rel related family of proteins performs a common function that is modulated by the carboxyl terminal domain. ..
  37. Madruga J, Koritschoner N, Diebold S, Kurz S, Zenke M. Polarised expression pattern of focal contact proteins in highly motile antigen presenting dendritic cells. J Cell Sci. 1999;112 ( Pt 11):1685-96 pubmed
    ..CD34(+ )stem cell-derived human dendritic cells also exhibited an elongated bipolar morphology, mode of migration and a polarised pattern of actin-vimentin expression similar to v-relER dendritic cells. ..
  38. Gelinas C, Temin H. The v-rel oncogene encodes a cell-specific transcriptional activator of certain promoters. Oncogene. 1988;3:349-55 pubmed
    ..Moreover, the extent of cell-specific transactivation by v-rel correlated with its toxic effect in these same cells. ..
  39. Narayanan R, Klement J, Ruben S, Higgins K, Rosen C. Identification of a naturally occurring transforming variant of the p65 subunit of NF-kappa B. Science. 1992;256:367-70 pubmed
    ..Thus, p65 delta, which associated weakly and interfered with DNA binding by p65, may sequester an essential limiting regulatory factor or factors required for NF-kappa B function. ..
  40. Inoue J, Kerr L, Ransone L, Bengal E, Hunter T, Verma I. c-rel activates but v-rel suppresses transcription from kappa B sites. Proc Natl Acad Sci U S A. 1991;88:3715-9 pubmed
    ..Thus, v-rel may interfere with the normal transcriptional machinery of the cell by acting as a dominant negative mutant. ..
  41. Boehmelt G, Madruga J, Dörfler P, Briegel K, Schwarz H, Enrietto P, et al. Dendritic cell progenitor is transformed by a conditional v-Rel estrogen receptor fusion protein v-RelER. Cell. 1995;80:341-52 pubmed
    ..Our studies therefore suggest that the conditional v-RelER, and probably also the authentic v-Rel, transform a common progenitor for neutrophils and dendritic cells. ..
  42. Diehl J, Hannink M. Identification of a C/EBP-Rel complex in avian lymphoid cells. Mol Cell Biol. 1994;14:6635-46 pubmed
    ..The identification of a protein complex that binds specifically to a consensus C/EBP site and contains both C/EBP and Rel family members suggests a novel mechanism for regulation of gene expression by Rel family proteins. ..
  43. Ishikawa H, Asano M, Kanda T, Kumar S, Gelinas C, Ito Y. Two novel functions associated with the Rel oncoproteins: DNA replication and cell-specific transcriptional activation. Oncogene. 1993;8:2889-96 pubmed
    ..The second promotes transcriptional activation in undifferentiated F9 cells and maps 3' to the RHR, a region essential for the transforming activity of v-Rel. ..
  44. Capobianco A, Gilmore T. A conditional mutant of vRel containing sequences from the human estrogen receptor. Virology. 1993;193:160-70 pubmed
    ..The vRel-Er protein may be useful for determining genes controlled by vRel. ..
  45. Bours V, Burd P, Brown K, Villalobos J, Park S, Ryseck R, et al. A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. Mol Cell Biol. 1992;12:685-95 pubmed
    ..The data imply the existence of a complex family of NF-kappa B-like transcription factors. ..
  46. Smardova J, Walker A, Morrison L, Kabrun N, Enrietto P. The role of the carboxy terminus of v-Rel in transformation and activation of endogenous gene expression. Oncogene. 1995;10:2017-26 pubmed
    ..Taken together, these results suggest that the carboxy terminus of v-Rel contains multiple sequences that participate in the activation of gene expression. ..
  47. Hannink M, Temin H. Transactivation of gene expression by nuclear and cytoplasmic rel proteins. Mol Cell Biol. 1989;9:4323-36 pubmed
    ..These results suggest that transactivation may be necessary but is not sufficient for transformation by rel proteins...
  48. Kralova J, Schatzle J, Liss A, Bargmann W, Bose H. Synergistic stimulation of avian I kappa B alpha transcription by rel and fos/jun factors. Oncogene. 1996;12:2595-604 pubmed
    ..These studies address the difference in c-Rel and v-Rel's ability to synergistically stimulate I kappa B alpha expression in conjunction with the AP-1 factors. ..
  49. Barth C, Ewert D, Olson W, Humphries E. Reticuloendotheliosis virus REV-T(REV-A)-induced neoplasia: development of tumors within the T-lymphoid and myeloid lineages. J Virol. 1990;64:6054-62 pubmed
    ..In 3-week-old cyclophosphamide-treated chicks, the presence of CIa+ CT-3- tumors bearing hematopoietic lineage markers, such as CLA-3 and 5M19, are most likely to have been derived from cells within the myeloid lineage. ..
  50. Matova N, Anderson K. Rel/NF-kappaB double mutants reveal that cellular immunity is central to Drosophila host defense. Proc Natl Acad Sci U S A. 2006;103:16424-9 pubmed
  51. Fan Y, Gelinas C. An optimal range of transcription potency is necessary for efficient cell transformation by c-Rel to ensure optimal nuclear localization and gene-specific activation. Oncogene. 2007;26:4038-43 pubmed
    ..These findings may have important implications for understanding how Rel TAD mutations can lead to a more oncogenic phenotype. ..
  52. Simek S, Rice N. Detection and characterization of the protein encoded by the chicken c-rel protooncogene. Oncogene Res. 1988;2:103-19 pubmed
    ..The c-rel protein is found in the soluble cytoplasmic fraction of chicken lymphoid cells and is not associated in any stable way with other cellular proteins. Unlike the viral protein, p68c-rel is not detectably phosphorylated...
  53. LaCasse E, Baird S, Korneluk R, MacKenzie A. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene. 1998;17:3247-59 pubmed
    ..Overall a picture consistent with an IAP role in tumour progression rather than tumour initiation is emerging making the IAPs an attractive therapeutic target. ..