Avian reticuloendotheliosis virus: Identification of the hematopoietic target cell for transformation

Lewis, Robert B.; McClure, Janela; Rup, Bonita; Niesel, David W.; Garry, Robert F.; Hoelzer, Jacalyn D.; Nazerian, K.; Bose, Henry R.

doi:10.1016/0092-8674(81)90060-x

Cited by 91 publications

(65 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, vRel-transformed cell lines, established by in vitro infection of chicken spleen cells and which do not shed helper virus, can induce fatal tumors with as few as 100 cells when injected into histocompatible chickens (Lewis et al, 1981). Cells transformed in vitro by v-Rel have been reported to have characteristics of immature pre-B/pre-T cells (Beug et al, 1981;Chen et al, 1988;Morrison et al, 1991;Zhang et al, 1989), abnormal B cells (Chen et al, 1988), immature and mature B cells (Benatar et al, 1991(Benatar et al, , 1992Boehmelt et al, 1995;Keller et al, 1979;Lewis et al, 1981;Sasaki and Koyama, 1989;Shibuya et al, 1982;Zhang et al, 1991), T cells (Barth et al, 1990;Marmor et al, 1993;Schat et al, 1992), myeloid cells (Barth et al, 1990;Morrison et al, 1991), erythroid cells (Morrison et al, 1991), and pre-dendritic cells (Boehmelt et al, 1995).…”

Section: V-rel As a Member Of The Rel/nf-kb Family Of Transcription Fmentioning

confidence: 99%

Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel

1999

View full text Add to dashboard Cite

The avian Rev-T retrovirus encodes the v-Rel oncoprotein, which is a member of the Rel/NF-kB transcription factor family. v-Rel induces a rapidly fatal lymphoma/ leukemia in young birds, and v-Rel can transform and immortalize a variety of avian cell types in vitro. Although Rel/NF-kB transcription factors have been associated with oncogenesis in mammals, v-Rel is the only member of this family that is frankly oncogenic in animal model systems. The potent oncogenicity of v-Rel is the consequence of a number of mutations that have altered its activity and regulation: for example, certain mutations decrease its ability to be regulated by IkBa, change its DNA-binding site speci®city, and endow it with new transactivation properties. The study of v-Rel will continue to increase our knowledge of how cellular Rel proteins contribute to oncogenesis by a ecting cell growth, altering cell-cycle regulation, and blocking apoptosis. 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-kB transcription factors.

show abstract

Section: V-rel As a Member Of The Rel/nf-kb Family Of Transcription Fmentioning

confidence: 99%

Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel

1999

View full text Add to dashboard Cite

show abstract

“…Conditioned media collected from DT40 cells contains high levels of VEGF detected by ELISA assay (Figure 5b), similar to that produced by P493-6 cells ( Figure 1a). In contrast, the E3 cell line, a bone marrow-derived B-cell precursor cell line transformed by an REV retrovirus (Lewis et al, 1981) expressed undetectable Myc levels in 20 mg of cell lysate (Figure 5a), and produced low levels of VEGF ( Figure 5b). Similar findings were obtained using the 1W41 REV-transformed B-cell line, which also showed background VEGF levels (data not shown).…”

Section: Myc Also Regulates Vegf Production In Avian Lymphocytesmentioning

confidence: 99%

Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation

et al. 2004

View full text Add to dashboard Cite

“…REV-T induces rapidly growing lymphoid tumors in the spleen and liver of infected galliform birds and solid tumors in their connective tissue (Lewis et al, 1981;Moore and Bose, 1988;Robinson and Twiehaus, 1974). REV-T originated by the transduction of a turkey c-rel gene by a Reticuloendotheliosis associated virus (REV-A) (Breitman et al, 1980;Hoelzer et al, 1979;Wilhelmsen et al, 1984).…”

mentioning

confidence: 99%

“…Several Rel/NF-kB members and their IkB inhibitors have been implicated in the induction of various malignant processes (Fracchiolla et al, 1993;Kabrun et al, 1990;Lewis et al, 1981;Lu et al, 1991;Neri et al, 1991;Ohno et al, 1990). The cRel proto-oncoprotein itself can be transforming when overexpressed from a retroviral promoter (Abbadie et al, 1993;Diehl et al, 1993;Kralova et al, 1994;Mosialos et al, 1991;Nehyba et al, 1994).…”

mentioning

confidence: 99%

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

1997

View full text Add to dashboard Cite

The oncogene v-rel of Reticuloendotheliosis virus, strain T, is derived from an avian c-rel proto-oncogene. c-rel encodes a member of the Rel/NF-kB family of transcription factors. The highly oncogenic v-Rel di ers from c-Rel which has low transforming potential by the acquisition of numerous mutations. In this manuscript, we demonstrate that the oncogenic mutations in v-Rel directly alter the ability of this protein to bind to DNA. Electrophoretic mobility shift analysis with Rel proteins synthesized in vitro as well as isolated from nuclei of Rel expressing cells showed that three mutation clusters, present in the N-terminus, the center and the C-terminus of v-Rel, altered three di erent aspects of DNA binding. In contrast, the oncogenic C-terminal deletion of 118 amino acids present in v-Rel had almost no in¯uence on its DNA binding. The N-terminal mutation cluster altered the kB DNA-binding speci®city of the v-Rel oncoprotein relative to c-Rel. The mutation Met-20?Thr was found to be principally responsible for this alteration. The second mutation cluster was responsible for increased binding of v-Rel to all the kB sites examined presumably because it stabilized v-Rel homodimers. This alteration in DNA binding was mapped to the group of two mutations within the cluster. In contrast, the third mutation cluster in the C-terminus of v-Rel destabilized the binding of v-Rel to all of the kB sites examined. This is the ®rst indication that regions outside the Rel Homology Region can participate in the control of binding of the c-Rel protein to DNA. The three mutation clusters examined contributed to the tumorigenic potential of v-Rel with the relative strength decreasing with their position from the N-terminus to the C-terminus. These results suggest that the oncogenic mutations in v-Rel cooperate and enable v-Rel to form nuclear complexes with aberrant DNA-binding properties that may directly alter gene expression and DNA replication resulting in the transformation of the cell.

show abstract

Avian reticuloendotheliosis virus: Identification of the hematopoietic target cell for transformation

Cited by 91 publications

References 43 publications

Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel

Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel

Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation

Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein

Contact Info

Product

Resources

About