Genomes and Genes
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.
- 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. ..
- 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...
- Gilmore T. The Re1/NF-kappa B/I kappa B signal transduction pathway and cancer. Cancer Treat Res. 2003;115:241-65 pubmed
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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
- 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. ..
- 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. ..
- 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. ..
- 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
- 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
- Dushay M, Eldon E. Drosophila immune responses as models for human immunity. Am J Hum Genet. 1998;62:10-4 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Sif S, Gilmore T. Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1. J Virol. 1994;68:7131-8 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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
- 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. ..
- 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...
- 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. ..