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  1. Article: DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective.

    Secchi, Massimiliano / Lodola, Camilla / Garbelli, Anna / Bione, Silvia / Maga, Giovanni

    Cancers

    2022  Volume 14, Issue 15

    Abstract: RNA helicases of the DEAD-box family are involved in several metabolic pathways, from transcription and translation to cell proliferation, innate immunity and stress response. Given their multiple roles, it is not surprising that their deregulation or ... ...

    Abstract RNA helicases of the DEAD-box family are involved in several metabolic pathways, from transcription and translation to cell proliferation, innate immunity and stress response. Given their multiple roles, it is not surprising that their deregulation or mutation is linked to different pathological conditions, including cancer. However, while in some cases the loss of function of a given DEAD-box helicase promotes tumor transformation, indicating an oncosuppressive role, in other contexts the overexpression of the same enzyme favors cancer progression, thus acting as a typical oncogene. The roles of two well-characterized members of this family, DDX3X and DDX5, as both oncogenes and oncosuppressors have been documented in several cancer types. Understanding the interplay of the different cellular contexts, as defined by the molecular interaction networks of DDX3X and DDX5 in different tumors, with the cancer-specific roles played by these proteins could help to explain their apparently conflicting roles as cancer drivers or suppressors.
    Language English
    Publishing date 2022-08-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14153820
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From the magic bullet to the magic target: exploiting the diverse roles of DDX3X in viral infections and tumorigenesis.

    Riva, Valentina / Maga, Giovanni

    Future medicinal chemistry

    2019  Volume 11, Issue 11, Page(s) 1357–1381

    Abstract: DDX3X is an ATPase/RNA helicase of the DEAD-box family and one of the most multifaceted helicases known up to date, acting in RNA metabolism, cell cycle control, apoptosis, stress response and innate immunity. Depending on the virus or the viral cycle ... ...

    Abstract DDX3X is an ATPase/RNA helicase of the DEAD-box family and one of the most multifaceted helicases known up to date, acting in RNA metabolism, cell cycle control, apoptosis, stress response and innate immunity. Depending on the virus or the viral cycle stage, DDX3X can act either in a proviral fashion or as an antiviral factor. Similarly, in different cancer types, it can act either as an oncogene or a tumor-suppressor gene. Accumulating evidence indicated that DDX3X can be considered a promising target for anticancer and antiviral chemotherapy, but also that its exploitation requires a deeper understanding of the molecular mechanisms underlying its dual role in cancer and viral infections. In this Review, we will summarize the known roles of DDX3X in different tumor types and viral infections, and the different inhibitors available, illustrating the possible advantages and potential caveats of their use as anticancer and antiviral drugs.
    MeSH term(s) Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Carcinogenesis/drug effects ; Carcinogenesis/genetics ; Carcinogenesis/immunology ; Carcinogenesis/metabolism ; Cell Proliferation/drug effects ; DEAD-box RNA Helicases/chemistry ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/immunology ; DEAD-box RNA Helicases/metabolism ; Drug Discovery ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Humans ; Immunity, Innate/drug effects ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Virus Diseases/drug therapy ; Virus Diseases/genetics ; Virus Diseases/immunology ; Virus Diseases/metabolism ; Viruses/drug effects ; Viruses/immunology
    Chemical Substances Antineoplastic Agents ; Antiviral Agents ; Enzyme Inhibitors ; DDX3X protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2019-02-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1756-8927
    ISSN (online) 1756-8927
    DOI 10.4155/fmc-2018-0451
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Foreword: "new targets and new drugs: from in silico planning to in vivo testing".

    Maga, Giovanni

    Current pharmaceutical biotechnology

    2012  Volume 14, Issue 5, Page(s) 475–476

    MeSH term(s) Computer Simulation ; Drug Delivery Systems ; Drug Design ; Humans ; Pharmaceutical Preparations
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2012-03-09
    Publishing country Netherlands
    Document type Introductory Journal Article
    ZDB-ID 2132197-8
    ISSN 1873-4316 ; 1389-2010
    ISSN (online) 1873-4316
    ISSN 1389-2010
    DOI 10.2174/138920101405131111103331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book: AIDS

    Maga, Giovanni

    la verità negata : come l'HIV causa l'AIDS e perché dall'AIDS si potrà guarire

    (Informa)

    2014  

    Author's details Giovanni Maga
    Series title Informa
    MeSH term(s) Acquired Immunodeficiency Syndrome ; HIV Infections
    Language Italian
    Size ix, 119 pages :, illustrations ;, 21 cm.
    Edition Prima edizione.
    Document type Book
    ISBN 9788849004809 ; 884900480X
    Database Catalogue of the US National Library of Medicine (NLM)

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  5. Article ; Online: Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA.

    Lodola, Camilla / Secchi, Massimiliano / Sinigiani, Virginia / De Palma, Antonella / Rossi, Rossana / Perico, Davide / Mauri, Pier Luigi / Maga, Giovanni

    International journal of molecular sciences

    2023  Volume 24, Issue 6

    Abstract: The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np ... ...

    Abstract The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.
    MeSH term(s) Humans ; RNA Helicases ; RNA, Double-Stranded ; SARS-CoV-2 ; COVID-19 ; Nucleocapsid Proteins ; DEAD-box RNA Helicases/genetics
    Chemical Substances RNA Helicases (EC 3.6.4.13) ; RNA, Double-Stranded ; Nucleocapsid Proteins ; DDX3X protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13) ; DDX1 protein, human (EC 3.6.1.-)
    Language English
    Publishing date 2023-03-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24065784
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Identification and Biological Characterization of the Pyrazolo[3,4-

    Contadini, Claudia / Cirotti, Claudia / Carbone, Anna / Norouzi, Mehrdad / Cianciusi, Annarita / Crespan, Emmanuele / Perini, Cecilia / Maga, Giovanni / Barilà, Daniela / Musumeci, Francesca / Schenone, Silvia

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 7

    Abstract: Src is a non-receptor tyrosine kinase (TK) whose involvement in cancer, including glioblastoma (GBM), has been extensively demonstrated. In this context, we started from ... ...

    Abstract Src is a non-receptor tyrosine kinase (TK) whose involvement in cancer, including glioblastoma (GBM), has been extensively demonstrated. In this context, we started from our
    Language English
    Publishing date 2023-07-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16070958
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Biological Evaluation and In Vitro Characterization of ADME Profile of In-House Pyrazolo[3,4-

    Poggialini, Federica / Vagaggini, Chiara / Brai, Annalaura / Pasqualini, Claudia / Crespan, Emmanuele / Maga, Giovanni / Perini, Cecilia / Cabella, Noemi / Botta, Lorenzo / Musumeci, Francesca / Frosini, Maria / Schenone, Silvia / Dreassi, Elena

    Pharmaceutics

    2023  Volume 15, Issue 2

    Abstract: The therapeutic use of tyrosine kinase inhibitors (TKIs) represents one of the successful strategies for the treatment of glioblastoma (GBM). Pyrazolo[3,4- ...

    Abstract The therapeutic use of tyrosine kinase inhibitors (TKIs) represents one of the successful strategies for the treatment of glioblastoma (GBM). Pyrazolo[3,4-
    Language English
    Publishing date 2023-01-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15020453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Host DDX Helicases as Possible SARS-CoV-2 Proviral Factors: A Structural Overview of Their Hijacking Through Multiple Viral Proteins.

    Squeglia, Flavia / Romano, Maria / Ruggiero, Alessia / Maga, Giovanni / Berisio, Rita

    Frontiers in chemistry

    2020  Volume 8, Page(s) 602162

    Abstract: As intracellular parasites, viruses hijack the host cell metabolic machinery for their replication. Among other cellular proteins, the DEAD-box (DDX) RNA helicases have been shown to be hijacked by coronaviruses and to participate in essential DDX- ... ...

    Abstract As intracellular parasites, viruses hijack the host cell metabolic machinery for their replication. Among other cellular proteins, the DEAD-box (DDX) RNA helicases have been shown to be hijacked by coronaviruses and to participate in essential DDX-mediated viral replication steps. Human DDX RNA helicases play essential roles in a broad array of biological processes and serve multiple roles at the virus-host interface. The viral proteins responsible for DDX interactions are highly conserved among coronaviruses, suggesting that they might also play conserved functions in the SARS-CoV-2 replication cycle. In this review, we provide an update of the structural and functional data of DDX as possible key factors involved in SARS-CoV-2 hijacking mechanisms. We also attempt to fill the existing gaps in the available structural information through homology modeling. Based on this information, we propose possible paths exploited by the virus to replicate more efficiently by taking advantage of host DDX proteins. As a general rule, sequestration of DDX helicases by SARS-CoV-2 is expected to play a pro-viral role in two ways: by enhancing key steps of the virus life cycle and, at the same time, by suppressing the host innate immune response.
    Language English
    Publishing date 2020-12-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2711776-5
    ISSN 2296-2646
    ISSN 2296-2646
    DOI 10.3389/fchem.2020.602162
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Novel Insights into the Biochemical Mechanism of CK1ε and its Functional Interplay with DDX3X.

    Bono, Bartolo / Franco, Giulia / Riva, Valentina / Garbelli, Anna / Maga, Giovanni

    International journal of molecular sciences

    2020  Volume 21, Issue 17

    Abstract: Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA ... ...

    Abstract Casein Kinase 1 epsilon (CK1ε) is a member of the serine (Ser)/threonine (Thr) CK1 family, known to have crucial roles in several biological scenarios and, ever more frequently, in pathological contexts, such as cancer. Recently, the human DEAD-box RNA helicase 3 X-linked (DDX3X), involved in cancer proliferation and viral infections, has been identified as one of CK1ε substrates and its positive regulator in the Wnt/β-catenin network. However, the way by which these two proteins influence each other has not been fully clarified. In order to further investigate their interplay, we defined the kinetic parameters of CK1ε towards its substrates: ATP, casein, Dvl2 and DDX3X. CK1ε affinity for ATP depends on the nature of the substrate: increasing of casein concentrations led to an increase of Km
    MeSH term(s) Adenosine Triphosphate/metabolism ; Casein Kinase Iepsilon/genetics ; Casein Kinase Iepsilon/metabolism ; Caseins/metabolism ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism ; Humans ; Kinetics ; Phosphorylation ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances CTNNB1 protein, human ; Caseins ; Wnt Proteins ; beta Catenin ; Adenosine Triphosphate (8L70Q75FXE) ; Casein Kinase Iepsilon (EC 2.7.11.1) ; DDX3X protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Keywords covid19
    Language English
    Publishing date 2020-09-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21176449
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA

    Camilla Lodola / Massimiliano Secchi / Virginia Sinigiani / Antonella De Palma / Rossana Rossi / Davide Perico / Pier Luigi Mauri / Giovanni Maga

    International Journal of Molecular Sciences, Vol 24, Iss 5784, p

    2023  Volume 5784

    Abstract: The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np ... ...

    Abstract The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.
    Keywords SARS-CoV-2 ; dead-box RNA helicase ; RNA binding ; nucleocapsid ; DDX3X ; DDX1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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