Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Fu, Wenli; Verma, Dinesh; Burton, Ashlee Danielle; Swaminathan, Sankar

doi:10.1128/jvi.01244-18

Cited by 18 publications

(14 citation statements)

References 58 publications

(122 reference statements)

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“…The role of DDX3 in oncogenesis is related to the regulation of cell growth, cell cycle, and cell survival. Increased DDX3 expression promotes cancer cell growth in medulloblastoma, colorectal, breast, prostate, and lung cancer [ 20 , 44 , 45 , 46 ], whereas depletion of DDX3 induces cell cycle arrest in the G1 phase in cancer cells of those cancers ( Table 1 ) [ 20 , 31 , 47 , 48 , 49 ]. Knockdown of DDX3 also inhibits cell cycle progression by blocking entry into the S phase.…”

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

“…DHX9, as a multifunctional protein, regulates transcription, translation, miRNA processing, RNA transport, and genome maintenance processes [ 7 , 8 , 13 , 45 ]. DHX9 is overexpressed in several types of human cancers, including cervical cancer, breast cancer, prostate cancer, colorectal cancer, hepatocellular carcinoma, and Ewing sarcoma [ 56 , 57 , 58 , 59 ].…”

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

“…Mechanically, DHX33 recruits active RNA polymerase II (Pol II) to the promoters of many cell-cycle-related genes, including cyclin E2, cyclin D1, E2F1, MMP9, MCMs, CDC6, and CDC20, and initiates the transcription of those genes [53,55] (Figure 3). DHX9, as a multifunctional protein, regulates transcription, translation, miRNA processing, RNA transport, and genome maintenance processes [7,8,13,45]. DHX9 is overexpressed in several types of human cancers, including cervical cancer, breast cancer, prostate cancer, colorectal cancer, hepatocellular carcinoma, and Ewing sarcoma [56][57][58][59].…”

Section: Rna Helicases Regulate G1-s Phase Transitionmentioning

confidence: 99%

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DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Zhang

2021

Cells

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Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell cycle regulation has been linked to many diseases. Thus, there is an urgent need to understand the diverse molecular mechanisms of how the cell cycle is controlled. RNA helicases constitute a large family of proteins with functions in all aspects of RNA metabolism, including unwinding or annealing of RNA molecules to regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, or remodeling ribonucleoprotein complexes, to regulate gene expression. RNA helicases also regulate the activity of specific proteins through direct interaction. Abnormal expression of RNA helicases has been associated with different diseases, including cancer, neurological disorders, aging, and autosomal dominant polycystic kidney disease (ADPKD) via regulation of a diverse range of cellular processes such as cell proliferation, cell cycle arrest, and apoptosis. Recent studies showed that RNA helicases participate in the regulation of the cell cycle progression at each cell cycle phase, including G1-S transition, S phase, G2-M transition, mitosis, and cytokinesis. In this review, we discuss the essential roles and mechanisms of RNA helicases in the regulation of the cell cycle at different phases. For that, RNA helicases provide a rich source of targets for the development of therapeutic or prophylactic drugs. We also discuss the different targeting strategies against RNA helicases, the different types of compounds explored, the proposed inhibitory mechanisms of the compounds on specific RNA helicases, and the therapeutic potential of these compounds in the treatment of various disorders.

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Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

Section: Rna Helicases Regulate G1-s Phase Transitionmentioning

confidence: 99%

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DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Zhang

2021

Cells

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“…It also takes part in the virus life cycle to regulate viral RNA synthesis by interacting with N protein of porcine reproductive and respiratory syndrome virus [32]. DHX9 is a component of virus replication complexes of chikungunya virus (KSHV) and also EBV and hepatitis B virus [33][34][35]. KAP1 is a ubiquitously expressed protein involved in many critical functions which are dependent upon post-translational modifications, such as phosphorylation or sumoylation [36].…”

Section: Discussionmentioning

confidence: 99%

The interactome of porcine epidemic diarrhea virus nucleocapsid protein

Tan

Ding

Cai

et al. 2019

Preprint

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Background Many viral proteins specifically interact with cellular proteins to facilitate virus replication. Understanding these interactions can decipher the viral infection mechanism and provide potential targets for antiviral therapy. Porcine epidemic diarrhea virus (PEDV), the agent of PED, causes numerous economic losses for the swine industry each year. Till now, no effective vaccine or drugs are available to contain this disease. As a result, it is critical urgent to elucidate the PEDV interactome. The nucleocapsid (N) of PEDV plays an important role in viral replication. Results In this study, the N gene was cloned into pEGFP-C1 and transfected into 293T cells. The interactome of N was elucidated by label-free mass spectrometry. A total of 125 cellular proteins interacting with PEDV N protein were discovered, of which 4 cellular proteins, DHX9, NCL, KAP1, TCEA1, were confirmed by pull down, immunoprecipitation, and co-localization. Conclusions The interactome of N protein supplied a powerful tool to explore the role of N in PEDV infection and therapeutic targets.

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“…Several unanswered questions concerning the roles and mechanism of SM in EBV replication and innate immune modulation arise when we consider this finding together with current literature. SM can inhibit several viral and cellular regulators of viral replication and innate immunity including RNA helicase DHX9 [126], which is known to be important in the repression of innate immunity. In particular, DHX9 is critically involved in DNA and RNA sensing [127,128].…”

Section: Ebv Perturbation Of Ifn Signalingmentioning

confidence: 99%

Epstein–Barr Virus and Innate Immunity: Friends or Foes?

et al. 2019

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Epstein–Barr virus (EBV) successfully persists in the vast majority of adults but causes lymphoid and epithelial malignancies in a small fraction of latently infected individuals. Innate immunity is the first-line antiviral defense, which EBV has to evade in favor of its own replication and infection. EBV uses multiple strategies to perturb innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like, and AIM2-like receptors as well as cyclic GMP-AMP synthase. EBV also counteracts interferon production and signaling, including TBK1-IRF3 and JAK-STAT pathways. However, activation of innate immunity also triggers pro-inflammatory response and proteolytic cleavage of caspases, both of which exhibit proviral activity under some circumstances. Pathogenic inflammation also contributes to EBV oncogenesis. EBV activates NFκB signaling and induces pro-inflammatory cytokines. Through differential modulation of the proviral and antiviral roles of caspases and other host factors at different stages of infection, EBV usurps cellular programs for death and inflammation to its own benefits. The outcome of EBV infection is governed by a delicate interplay between innate immunity and EBV. A better understanding of this interplay will instruct prevention and intervention of EBV-associated cancers.

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Cellular RNA Helicase DHX9 Interacts with the Essential Epstein-Barr Virus (EBV) Protein SM and Restricts EBV Lytic Replication

Cited by 18 publications

References 58 publications

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

The interactome of porcine epidemic diarrhea virus nucleocapsid protein

Epstein–Barr Virus and Innate Immunity: Friends or Foes?

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