High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro

Abbadie, Corinne; Kabrun, N; Bouali, Fatima; Šmardová, Jana; Stéhelin, D; Vandenbunder, Bernard; Enrietto, Paula J.

doi:10.1016/0092-8674(93)90534-w

Cited by 215 publications

(154 citation statements)

References 45 publications

Supporting

Mentioning

140

Contrasting

Order By: Relevance

“…As reported earlier, overexpression of c-rel morphologically transforms CEFs (Abbadie et al, 1993;Kralova et al, 1994). Although c-rel ®broblasts do not form colonies in soft agar, they do display characteristic disruption of cellular cytoskeleton and a remarkable extension of life span.…”

Section: Characterization Of Viral-transduced ®Broblastssupporting

confidence: 72%

“…Because these cell lines also contain truncated forms of c-Rel (Hrdlickova et al, 1994), it is not clear if transcriptional activation and transformation in both of them result from wild-type or mutant c-Rel activity. We previously reported that overexpression of wild-type c-Rel in bone marrow cells, which appear to be granulocytic in origin (unpublished observation), leads to cell death (Abbadie et al, 1993). For this reason, it will be important to determine if the genes identi®ed in this study are upregulated in the granulocytic bone marrow target prior to the onset of cell death.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Characterization of changes in gene expression associated with malignant transformation by the NF-κB family member, v-Rel

1997

View full text Add to dashboard Cite

Section: Characterization Of Viral-transduced ®Broblastssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 92%

Characterization of changes in gene expression associated with malignant transformation by the NF-κB family member, v-Rel

1997

View full text Add to dashboard Cite

“…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). Transformation, particularly of lymphoid cells, by c-Rel is, however, very weak.…”

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

“…Previous studies have shown that overexpression of cRel morphologically transforms primary avian fibroblasts and confers a distinctive phenotype on these cells, characterized by altered morphology, extensive disruption of cellular cytoskeleton, and an extended life span (Abbadie et al, 1993;Kralova et al, 1994). To determine if expression of c-RelER induces a similar phenotype, c-RelER ®broblasts were grown in the presence or absence of estrogen.…”

Section: Expression Of C-reler In Chicken Embryo ®Broblastsmentioning

confidence: 99%

“…However, c-Rel and its mutated viral homolog, v-Rel, are the only members of the family consistently shown to be oncogenic in vivo (Gilmore et al, 1996). Moreover, depending on the cell type, overexpression of c-Rel can lead either to transformation or programmed cell death (Abbadie et al, 1993). The mechanisms of these processes remain unclear, although most data available to-date indicate that they result from aberrant gene expression induced by Rel (Gilmore et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

A chicken c-Rel-estrogen receptor chimeric protein shows conditional nuclear localization, DNA binding, transformation and transcriptional activation

et al. 1998

View full text Add to dashboard Cite

In this report, we characterize the biological and biochemical properties of a conditional protein containing chicken c-Rel fused to the hormone-binding domain of the human estrogen receptor. This chimeric c-RelER protein causes estrogen-dependent, but otherwise c-Relspeci®c, transformation of avian ®broblasts in vitro. Our results demonstrate that c-RelER heterodimerizes with wild-type c-Rel and forms speci®c complexes with IkB-a. Estrogen causes translocation of c-RelER to the nucleus and stabilizes its binding to DNA. Hormone-activated cRelER induces transcription of at least four cellular genes that are constitutively active in wild-type c-Reltransformed ®broblasts. Two distinct cell populations were examined that di ered with respect to their growth phenotypes. The growth of ®broblasts with moderate expression levels of c-RelER was stimulated by estrogen. In contrast, the addition of estrogen to cells with high cRelER expression levels resulted in inhibition of cytokinesis and the arrest of growth. The carboxy terminal transactivation domain of c-Rel was required for the induction of these e ects since neither v-Rel nor c-Rel deletion mutants were able to induce similar changes. Taken together, our results demonstrate that high levels of c-Rel expression can a ect cell cycle control and/or cytokinesis. Furthermore, they also indicate that the biological properties of c-Rel in cell growth and di erentiation will potentially di er depending on the level of expression.

show abstract

High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro

Cited by 215 publications

References 45 publications

Characterization of changes in gene expression associated with malignant transformation by the NF-κB family member, v-Rel

Characterization of changes in gene expression associated with malignant transformation by the NF-κB family member, v-Rel

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

A chicken c-Rel-estrogen receptor chimeric protein shows conditional nuclear localization, DNA binding, transformation and transcriptional activation

Contact Info

Product

Resources

About