Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress

Coronel, Luis; Riege, Konstantin; Schwab, Katjana; Förste, Silke; Häckes, David; Semerau, Lena; Bernhart, Stephan H.; Siebert, Reiner; Hoffmann, Steve; Fischer, Martin

doi:10.1093/nar/gkab575

Cited by 28 publications

(60 citation statements)

References 96 publications

(152 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead, a large number of ΔNp63 targets were cell cycle genes, but the mechanistic link between ΔNp63 and the cell cycle remained unclear ( 10 , 32 ). Most recently, TargetGeneReg enabled the discovery of the transcription factor RFX7, an emerging tumor suppressor, as a novel node in the p53 GRN, proposing a mechanism for how p53 regulates several targets ( 33 ). RFX7 is linked to multiple lymphoid cancers ( 34 ), such as Burkitt lymphoma where we and others identified RFX7 as a potential cancer driver ( 35 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation

et al. 2022

Self Cite

View full text Add to dashboard Cite

In recent years, our web-atlas at www.TargetGeneReg.org has enabled many researchers to uncover new biological insights and to identify novel regulatory mechanisms that affect p53 and the cell cycle – signaling pathways that are frequently dysregulated in diseases like cancer. Here, we provide a substantial upgrade of the database that comprises an extension to include non-coding genes and the transcription factors ΔNp63 and RFX7. TargetGeneReg 2.0 combines gene expression profiling and transcription factor DNA binding data to determine, for each gene, the response to p53, ΔNp63, and cell cycle signaling. It can be used to dissect common, cell type and treatment-specific effects, identify the most promising candidates, and validate findings. We demonstrate the increased power and more intuitive layout of the resource using realistic examples.

show abstract

Section: Introductionmentioning

confidence: 99%

TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, reporter gene assays did not confirm p53-mediated activation through this locus [ 19 ]. We recently identified DDIT4 as a potential target of the novel p53-RFX7 signaling pathway [ 31 ]. Given these conflicting data, we investigated whether DDIT4 induction by p53 is mediated indirectly via RFX7.…”

Section: Resultsmentioning

confidence: 99%

“…Upper black tracks display publicly available p53 binding signals from Nutlin-3a-treated U2OS [ 40 ] and HCT116 [ 39 ] cells. Gray and orange tracks display RFX7 binding signals from respective dimethyl sulfoxide (DMSO) and Nutlin-3a-treated U2OS, HCT116, and RPE-1 cells [ 31 ]. B ChIP-qPCR of p53 and RFX7 binding to GAPDH (negative control), MDM2 (p53 positive control), and DDIT4 from U2OS cells treated with 10 µM Nutlin-3a or DMSO solvent control.…”

Section: Resultsmentioning

confidence: 99%

“…The emerging tumor suppressor RFX7, a putative cancer driver in Burkitt lymphoma [ 27 , 28 ] that was previously associated with multiple lymphoid neoplasms [ 29 ], up-regulates Ddit4 and inhibits mTORC1 activity in murine lymphoid cells [ 30 ]. Most recently, we found that p53 activates RFX7 through the induction of a lower migrating form, and we identified DDIT4 as a potential target of RFX7 also in human cells [ 31 ]. We now demonstrate that DDIT4 is indirectly up-regulated by p53 through the novel tumor suppressor RFX7 in human cell line models.…”

Section: Introductionmentioning

confidence: 99%

“…RFX7 ChIP-seq data is accessible through GEO series accession number GSE162184 [ 31 ]. p53 ChIP-seq data was obtained from CistromeDB [ 38 ], IDs 82544 [ 39 ], and 33077 [ 40 ].…”

mentioning

confidence: 99%

See 2 more Smart Citations

p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance

et al. 2021

Self Cite

View full text Add to dashboard Cite

In recent years the tumor suppressor p53 has been increasingly recognized as a potent regulator of the cell metabolism and for its ability to inhibit the critical pro-survival kinases AKT and mTOR. The mechanisms through which p53 controls AKT and mTOR, however, are largely unclear. Here, we demonstrate that p53 activates the metabolic regulator DDIT4 indirectly through the regulatory factor X 7 (RFX7). We provide evidence that DDIT4 is required for p53 to inhibit mTOR complex 2 (mTORC2)-dependent AKT activation. Most strikingly, we also find that the DDIT4 regulator RFX7 is required for p53-mediated inhibition of mTORC1 and AKT. Our results suggest that AMPK activation plays no role and p53-mediated AKT inhibition is not critical for p53-mediated mTORC1 inhibition. Moreover, using recently developed physiological cell culture media we uncover that basal p53 and RFX7 activity can play a critical role in restricting mTORC1 activity under physiological nutrient conditions, and we propose a nutrient-dependent model for p53-RFX7-mediated mTORC1 inhibition. These results establish RFX7 and its downstream target DDIT4 as essential effectors in metabolic control elicited by p53.

show abstract

The landscape of human p53‐regulated long non‐coding RNAs reveals critical host gene co‐regulation

2023

Self Cite

View full text Add to dashboard Cite

The role of long non-coding RNAs (lncRNAs) in p53-mediated tumor suppression has become increasingly appreciated in the past decade. Thus, the identification of p53-regulated lncRNAs can be a promising starting point to select and prioritize lncRNAs for functional analyses. By integrating transcriptome and transcription factor-binding data, we identified 379 lncRNAs that are recurrently differentially regulated by p53. Dissecting the mechanisms by which p53 regulates many of them, we identified sets of lncRNAs regulated either directly by p53 or indirectly through the p53-RFX7 and p53-p21-DREAM/RB:E2F pathways. Importantly, we identified multiple p53-responsive lncRNAs that are co-regulated with their protein-coding host genes, revealing an important mechanism by which p53 may regulate lncRNAs. Further analysis of transcriptome data and clinical data from cancer patients showed that recurrently p53-regulated lncRNAs are associated with patient survival. Together, the integrative analysis of the landscape of p53-regulated lncRNAs provides a powerful resource facilitating the identification of lncRNA function and displays the mechanisms of p53-dependent regulation that could be exploited for developing anticancer approaches.

show abstract

Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress

Cited by 28 publications

References 96 publications

TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation

TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation

p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance

The landscape of human p53‐regulated long non‐coding RNAs reveals critical host gene co‐regulation

Contact Info

Product

Resources

About