The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA

Geißler, Verena; Altmeyer, Simone; Stein, Barbara R.; Uhlmann‐Schiffler, Heike; Stahl, Hans

doi:10.1093/nar/gkt538

Cited by 34 publications

(37 citation statements)

References 89 publications

(86 reference statements)

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“…4,5 Because it is an ATPdependent RNA helicase, p68 can manipulate RNA structures, including pre-mRNA, rRNA, and microRNA. [6][7][8][9][10][11] P68 could also act as a transcriptional coactivator of several cancer-associated transcription factors, such as p53 tumor suppressor, 11 β-catenin, 12 and the androgen receptor, 13 which plays an essential role in cell proliferation, oncogenesis, and early stage organ development. 14 Indeed, p68 is aberrantly expressed or modified in different types of tumors, including breast, prostate, and colon cancer.…”

Section: Introductionmentioning

confidence: 99%

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5

Wang

Bao

et al. 2018

Cancer Science

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Gliomas are the most common central nervous system tumors. They show malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the nuclear factor‐κB signaling pathway by a downstream molecular mechanism that remains incompletely understood. In this study, we found that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68, using microarray analysis, and that p68 negatively regulates DUSP5. Upregulating DUSP5 in stably expressing cell lines (U87 and LN‐229) suppressed proliferation, invasion, and migration in glioma cells in vitro, consistent with the downregulation of p68. Furthermore, upregulating DUSP5 inhibited ERK phosphorylation, whereas downregulating DUSP5 rescued the level of ERK phosphorylation, indicating that DUSP5 might negatively regulate ERK signaling. Additionally, we show that DUSP5 levels were lower in high‐grade glioma than in low‐grade glioma. These results suggest that the p68‐induced negative regulation of DUSP5 promoted invasion by glioma cells and mediated the activation of the ERK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5

Wang

Bao

et al. 2018

Cancer Science

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“…Dbp2, a DEAD-box helicase which, like Dbp6 is involved in ribosome biogenesis, manifests a two-hybrid interaction with Upf1 10 and functions in the NMD pathway 57 . Recently, p68/DDX5, the human Dbp2 orthologue, was shown to interact with human UPF3 and to enhance the NMD-dependent degradation of its own mRNA, as well as mRNAs encoding DDX17 (another DEAD-box helicase highly similar to DDX5) and SMG-5, which are all characterized by long 3′-UTR regions 58 . Furthermore, the C-terminal fragment from human UPF2 (encompassing the mIF4G-3 domain and the region involved in UPF1-CH binding) was shown to interact with eIF4AI in a yeast two-hybrid assay 59 .…”

Section: Discussionmentioning

confidence: 99%

A Highly Conserved Region Essential for NMD in the Upf2 N-Terminal Domain

Fourati

Roy

Millán

et al. 2014

Journal of Molecular Biology

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Upf1, Upf2, and Upf3 are the principal regulators of Nonsense-mediated mRNA Decay (NMD), a cytoplasmic surveillance pathway that accelerates the degradation of mRNAs undergoing premature translation termination. These three proteins interact with each other, the ribosome, the translation termination machinery, and multiple mRNA decay factors, but the precise mechanism allowing the selective detection and degradation of nonsense-containing transcripts remains elusive. Here we have determined the crystal structure of the N-terminal mIF4G domain from Saccharomyces cerevisiae Upf2 and identified a highly conserved region in this domain that is essential for NMD and independent of Upf2’s binding sites for Upf1 and Upf3. Mutations within this conserved region not only inactivate NMD, but also disrupt Upf2 binding to specific proteins, including Dbp6, a DEAD-box helicase. Although current models indicate that Upf2 functions principally as an activator of Upf1 and a bridge between Upf1 and Upf3, our data suggest that it may also serve as a platform for the association of additional factors that play roles in premature translation termination and NMD.

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“…Thereby, a short motif of the core NMD factor UPF3b binds to the EJC core factors and serves as a platform to assemble an active NMD complex ( 52 , 77 ). Two other DEAD box proteins DDX5 and DDX17 have also recently been described to interact with UPF3b and this interaction seems crucial for the degradation of a limited subset of NMD substrates ( 78 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanism and regulation of the nonsense-mediated decay pathway

2016

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The Nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs) but also regulates the abundance of a large number of cellular RNAs. The central role of NMD in the control of gene expression requires the existence of buffering mechanisms that tightly regulate the magnitude of this pathway. Here, we will focus on the mechanism of NMD with an emphasis on the role of RNA helicases in the transition from NMD complexes that recognize a PTC to those that promote mRNA decay. We will also review recent strategies aimed at uncovering novel trans-acting factors and their functional role in the NMD pathway. Finally, we will describe recent progress in the study of the physiological role of the NMD response.

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The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA

Cited by 34 publications

References 89 publications

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5

P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5

A Highly Conserved Region Essential for NMD in the Upf2 N-Terminal Domain

Mechanism and regulation of the nonsense-mediated decay pathway

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