DDX5 is a multifunctional co-activator of steroid hormone receptors

Wagner, Martin; Rid, Raphaela; Maier, Christina; Maier, Richard H.; Laimer, Martin; Hintner, Helmut; Bauer, Johann; Önder, Kamil

doi:10.1016/j.mce.2012.03.014

Cited by 21 publications

(11 citation statements)

References 80 publications

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“…LXRα, PPARγ and ESR1) and related coregulators (i.e. MED1, BRD8, KAT5, DDX5) which are known to be involved in the regulation of lipid homeostasis we have validated the results obtained with the PCR based focused microarray by a classical RT-PCR designed to detect LXRα and its coactivator MED1 32 , PPARγ and its coactivators BRD8 and KAT5 33 34 and ESR1 and its coactivator DDX5 35 . The results confirmed that the stimulation of HepG2 cells with p17 caused a significant up-regulation of the expression of LXRα and its coactivator MED1 ( Fig.…”

Section: Resultsmentioning

confidence: 67%

The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

Renga

Francisci

Carino

et al. 2015

Sci Rep

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Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This viral protein regulated mRNA expression of some NRs among which LXRα and its transcriptional co-activator MED1 were highly induced at mRNA level. Dissection of p17 downstream intracellular pathway demonstrated that p17 mediated activation of Jak/STAT signaling is responsible for the promoter dependent activation of LXR. The treatment of both HepG2 as well as primary hepatocytes with HIV p17 results in the transcriptional activation of LXR target genes (SREBP1c and FAS) and lipid accumulation. These effects are lost in HepG2 cells pre-incubated with a serum from HIV positive person who underwent a vaccination with a p17 peptide as well as in HepG2 cells pre-incubated with the natural LXR antagonist gymnestrogenin. These results suggest that HIV p17 affects NRs and their related signal transduction thus contributing to the progression of liver disease in HIV infected patients.

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Section: Resultsmentioning

confidence: 67%

The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

Renga

Francisci

Carino

et al. 2015

Sci Rep

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“…(5,6) DDX5 may also act in the regulation of gene transcription as transcriptional co-regulators with estrogen receptor-a, p53, androgen receptor, and b-catenin. (7)(8)(9)(10)(11) Increasing evidence suggests that DDX5 is overexpressed in a variety of malignancies, including colorectal cancer, breast cancer, prostate cancer, head and neck squamous cell carcinoma, glioma, and leukemia. (9,10,(12)(13)(14)(15)(16)(17)(18)(19) DDX5 is implicated in cancer development and progression by functioning in several key cellular activities of cancer cells, such as proliferation, migration, cytoskeletal reorganization, and epithelial-mesenchymal transition (EMT).…”

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confidence: 99%

DDX5 promotes proliferation and tumorigenesis of non‐small‐cell lung cancer cells by activating β‐catenin signaling pathway

et al. 2015

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The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase that is frequently overexpressed in various cancers and acts as a transcriptional co-activator of several transcription factors, including β-catenin. DDX5 is reported to be involved in cancer progression by promoting cell proliferation and epithelial–mesenchymal transition. However, the clinical significance and biological role of DDX5 in non-small-cell lung cancer (NSCLC) remain largely unknown. In this study, we examined the expression of DDX5 in clinical NSCLC samples, investigated its role in regulating NSCLC cell proliferation and tumorigenesis, and explored the possible molecular mechanism. We found that DDX5 was significantly overexpressed in NSCLC tissues as compared with the matched normal adjacent tissues. In addition, overexpression of DDX5 was associated with advanced clinical stage, higher Ki67 index, and shorter overall survival in NSCLC patients. Upregulation of DDX5 promoted proliferation of NSCLC cells in vitro and growth of NSCLC xenografts in vivo, whereas downregulation of DDX5 showed the opposite effects. Furthermore, DDX5 directly interacted with β-catenin, promoted its nuclear translocation, and co-activated the expression of cyclin D1 and c-Myc. β-catenin silencing significantly abrogated DDX5-induced cyclin D1 and c-Myc expression and proliferation in NSCLC cells. Interestingly, DDX5 and cyclin D1 expression followed positive correlation in the same set of NSCLC samples. These findings indicated that DDX5 played an important role in the proliferation and tumorigenesis of NSCLC cells by activating the β-catenin signaling pathway. Therefore, DDX5 may serve as a novel prognostic marker and potential therapeutic target in the treatment of NSCLC.

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“…DDX5 is a DEAD box RNA helicase, and also acts as a transcriptional co-factor to modulate the activity of several cell proliferation-promoting TFs ( Fuller-Pace, 2013 ). For example, DDX5 has been reported to promote E2F1-, p53-, Androgen receptor- and β-catenin-mediated transcription of genes controlling cell-cycle progression and DDR ( Nicol et al, 2013 ; Clark et al, 2013 ; Wagner et al, 2012 ; Bates et al, 2005 ; Mazurek et al, 2012 ). In addition, studies have reported the involvement of ncRNAs in regulating the co-activator activity of DDX5 ( Caretti et al, 2006 ).…”

Section: Resultsmentioning

confidence: 99%

The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

Hao

Zong

Sun

et al. 2020

eLife

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Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation.

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DDX5 is a multifunctional co-activator of steroid hormone receptors

Cited by 21 publications

References 80 publications

The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

DDX5 promotes proliferation and tumorigenesis of non‐small‐cell lung cancer cells by activating β‐catenin signaling pathway

The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

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