Methods for Assessing the In Vitro Transforming Activity of NF-κB Transcription Factor c-Rel and Related Proteins

Gilmore, Thomas D.; Gélinas, Céline

doi:10.1007/978-1-4939-2422-6_26

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…Moreover, in both RC-K8 and SUDHL2 cells, alteration of this balanced REL/NF-κB activity by re-expression of wild-type A20 induces apoptosis [35] or by re-expression of IκBα [21] or knockdown of p300ΔC-1087 [12, 13] slows cell growth. On a related note, high-level expression of REL/NF-κB has been shown to be toxic in several cases [37, 38], and several reports have shown that mutations that reduce the high transactivation activity of REL can enhance its transforming activity [30, 39-42]. Thus, at least in part, the decreased growth of RC-K8 and SUDHL2 cells following knockdown of p300ΔC-1087 may be due to toxic effects of the consequently increased REL/NF-κB activity.…”

Section: Discussionmentioning

confidence: 99%

Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma

Haery

Mussakhan

Waxman

et al. 2016

Leukemia & Lymphoma

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Mutations in histone acetyltransferases (HATs) are among the most common mutations in diffuse large B-cell lymphoma (DLBCL). We previously showed that two human DLBCL cell lines, RC-K8 and SUDHL2, express C-terminally truncated, HAT domain-deficient p300 proteins (p300ΔC) that are required for optimal cell proliferation. Microarray analysis of mRNA expression in RC-K8 cells following p300ΔC knockdown shows upregulation of NF-κB and p53 gene expression programs and down-regulation of a MYC gene expression program. Experiments indicate that these gene expression changes are due to inhibitory effects of p300ΔC on NF-κB activity and on p53 protein levels and stimulatory effects on MYC protein levels, suggesting that p300ΔC mutants enhance the proliferation of DLBCL cells by adjusting the transcriptional output of cell-specific oncoproteins. We propose that p300/CBP gene truncation represents a new class of oncogenic mutation that optimizes the activity of context-specific oncogenic transcription factors. We propose “oncogenic modifier” to describe such mutations.

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Section: Discussionmentioning

confidence: 99%

Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma

Haery

Mussakhan

Waxman

et al. 2016

Leukemia & Lymphoma

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Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation

Yao

Vasoya

Kgosana

et al. 2017

Journal of General Virology

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The v-rel oncoprotein encoded by reticuloendotheliosis virus T strain (Rev-T) is a member of the rel/NF-κB family of transcription factors capable of transformation of primary chicken spleen and bone marrow cells. Rapid transformation of avian haematopoietic cells by v-rel occurs through a process of deregulation of multiple protein-encoding genes through its direct effect on their promoters. More recently, upregulation of oncogenic miR-155 and its precursor pre-miR-155 was demonstrated in both Rev-T-infected chicken embryo fibroblast cultures and Rev-T-induced B-cell lymphomas. Through electrophoresis mobility shift assay and reporter analysis on the gga-miR-155 promoter, we showed that the v-rel-induced miR-155 overexpression occurred by the direct binding to one of the putative NF-κB binding sites. Using the v-rel-induced transformation model on chicken embryonic splenocyte cultures, we could demonstrate a dynamic increase in miR-155 levels during the transformation. Transcriptome profiles of lymphoid cells transformed by v-rel showed upregulation of miR-155 accompanied by downregulation of a number of putative miR-155 targets such as Pu.1 and CEBPβ. We also showed that v-rel could rescue the suppression of miR-155 expression observed in Marek’s disease virus (MDV)-transformed cell lines, where its functional viral homologue MDV-miR-M4 is overexpressed. Demonstration of gene expression changes affecting major molecular pathways, including organismal injury and cancer in avian macrophages transfected with synthetic mature miR-155, underlines its potential direct role in transformation. Our study suggests that v-rel-induced transformation involves a complex set of events mediated by the direct activation of NF-κB targets, together with inhibitory effects on microRNA targets.

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Methods for Assessing the In Vitro Transforming Activity of NF-κB Transcription Factor c-Rel and Related Proteins

Cited by 2 publications

References 32 publications

Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma

Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma

Activation of gga-miR-155 by reticuloendotheliosis virus T strain and its contribution to transformation

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