The Corepressor CTBP2 Is a Coactivator of Retinoic Acid Receptor/Retinoid X Receptor in Retinoic Acid Signaling

Bajpe, Prashanth Kumar; Heynen, Guus J.J.E.; Mittempergher, Lorenza; Grernrum, Wipawadee; Rink, Iris A. de; Nijkamp, Wouter; Beijersbergen, Roderick L.; Bernards, René; Huang, Sidong

doi:10.1128/mcb.01213-12

Cited by 24 publications

(24 citation statements)

References 47 publications

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“…The three latter genes are involved in retinoic acid signaling pathway regulation and are considered as essential for diaphragm development. Interestingly, CTBP2 has been shown as a potent coactivator of retinoic acid signaling pathway, which is a major pathway for diaphragm development . This is achieved through recruitment of p300/CREBBP histone acetyltransferases onto retinoic acid target genes promoters, creating a permissive chromatin environment for their transcription …”

Section: Discussionmentioning

confidence: 99%

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

et al. 2018

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“…Enriched CtBP2 expression has been reported in stem cells, and this protein has been demonstrated to have an important role in stem cell maintenance and the regulation of differentiation in ESCs [66]. CtBP2 has also been identified as a coactivator that is critical for retinoic acid (RA)-induced transcription in mouse F9 cells [67]. CtBP1 and CtBP2 have been reported to directly interact with PRDM16 and selectively mediate the repression [68].…”

Section: Discussionmentioning

confidence: 99%

Obesity-Associated MiR-342-3p Promotes Adipogenesis of Mesenchymal Stem Cells by Suppressing CtBP2 and Releasing C/EBPα from CtBP2 Binding

Wang

et al. 2015

Cell Physiol Biochem

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Background/Aims: The elucidation of the molecular mechanism of adipocyte differentiation in mesenchymal stem cells is of essential importance for the development of treatments for metabolic diseases, such as obesity and diabetes. Methods: The expression levels of miR-342-3p and carboxy-terminal binding protein 2 (CtBP2) were regulated by oligonucleotide transfection. Adipogenic differentiation was induced by adipogenic medium containing indomethacin, dexamethasone and 3-isobutyl-1-methylxanthine on day 12, as determined by Oil Red O staining and triglyceride concentration assay to assess intracellular lipid accumulation. The induction of adipocyte-specific transcription factors and markers was detected by qRT-PCR and western blot. The regulation of CtBP2 expression by miR-342-3p was determined by western blot, qRT-PCR, luciferase reporter assay, ChIP assay and functional experiments. Results: We revealed that miR-342-3p was enriched in the adipose tissue of obese mice, and its expression was significantly elevated during adipogenic differentiation in both human mesenchymal stem cells (hMSCs) and 3T3L1 cells. Using gain- and loss-of-function assays, we demonstrated that the overexpression of miR-342-3p markedly promoted the differentiation of hMSCs into an adipogenic lineage. Adipogenesis was significantly blocked by miR-342-3p downregulation. We identified and validated that CtBP2 was a direct target of miR-342-3p in this process. The effects of the inhibition of CtBP2 were similar to those of miR-342-5p overexpression on adipogenic differentiation, promoting the release of C/EBPα from CtBP2 binding. Conclusion: miR-342-3p is a powerful enhancer of the adipogenesis of human adipose-derived MSCs that acts by inhibiting CtBP2 and releasing the key adipogenic regulator C/EBPα from CtBP2 binding, subsequently activating the expression of adipogenic transcription factors and markers.

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“…Several mechanisms of resistance to RA have been described to date, including mutations in the ligandbinding domain of PML-RARa in APL patients (17) and the epigenetic silencing of the RARb receptor (18,19), which leads to the inability of RA to activate the pathway and hence to RA resistance. CTBP2, generally a corepressor protein, was identified as a positive cofactor of RAR-RXR in mouse F9 cells, and its suppression conferred resistance to RA (13). Using loss-offunction genetic screens Huang and colleagues showed that knockdown of the zinc finger protein ZNF423 leads to the loss of activation of RA target genes.…”

Section: Introductionmentioning

confidence: 99%

“…In the absence of RA, RAR/RXR is in complex with corepressors like NCoR, SMRT, and HDACs that repress the transcription of RA target genes (9,10). Binding of RA to RAR results in a conformational change of RAR, which leads to an exchange of repressor proteins for transcriptional coactivator proteins like CBP/p300, PCAF, CTBP2, and p160, enabling the transcription of RA target genes (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma

Heynen

Nevedomskaya

Palit

et al. 2016

Molecular Cancer Research

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Neuroblastoma cell lines can differentiate upon treatment with retinoic acid (RA), a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen, we identified an unexpected link between RA signaling and mastermindlike 3 (MAML3), a known transcriptional coactivator for NOTCH. Our findings indicate that MAML3 expression leads to the loss of activation of a subset of RA target genes, which hampers RA-induced differentiation and promotes resistance to RA. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the RA receptor, suggesting a direct role for MAML3 in the regulation of these genes. In addition, MAML3 has RA-independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. These results demonstrate an important mechanistic role for MAML3 in proliferation and RA-mediated differentiation.Implications: MAML3 coordinates transcription regulation with receptor tyrosine kinase pathway activation, shedding new light on why this gene is mutated in multiple cancers.

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The Corepressor CTBP2 Is a Coactivator of Retinoic Acid Receptor/Retinoid X Receptor in Retinoic Acid Signaling

Cited by 24 publications

References 47 publications

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

Obesity-Associated MiR-342-3p Promotes Adipogenesis of Mesenchymal Stem Cells by Suppressing CtBP2 and Releasing C/EBPα from CtBP2 Binding

Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma

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