c-Myc blazing a trail of death

coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    TRAIL ligand induces selectively apoptosis in tumor cells by binding to two death receptors (DR4 and DR5) and holds promise as a potential therapeutic agent against cancer. While it has been known for long time that TRAIL receptors are commonly expressed in wide variety of normal tissues, it is not well understood why TRAIL kills tumor cells but leaves normal cells unharmed. The prototypic oncogene c-Myc promotes the cell cycle and simultaneously primes activation of the Bcl-2 family controlled mitochondria apoptosis pathway. A striking reflection of the c-Myc-dependent apoptotic sensitization is the dramatic c-Myc-induced vulnerability of cells to TRAIL and other death receptor ligands. Here we summarize the recent findings regarding the death mechanisms of TRAIL/TRAIL receptor system and the connection of c-Myc to the mitochondrial apoptosis pathway, focusing on our work that couples c-Myc via Bak to the TRAIL death receptor pathway. Finally, we present a mitochondria-priming model to explain how c-Myc-Bak interaction amplifies the TRAIL-induced caspase 8-Bid pathway to induce full-blown apoptosis. We discuss the implications of these findings for understanding the selective cytotoxicity of TRAIL and for the therapeutic exploitation of the death receptor pathway.
    Original languageEnglish
    JournalCell Cycle
    Volume6
    Issue number20
    Pages (from-to)2464-2472
    Number of pages9
    ISSN1538-4101
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Cite this

    @article{36e8327a998d49ac9c593bfd4b67cb17,
    title = "c-Myc blazing a trail of death: coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc",
    abstract = "TRAIL ligand induces selectively apoptosis in tumor cells by binding to two death receptors (DR4 and DR5) and holds promise as a potential therapeutic agent against cancer. While it has been known for long time that TRAIL receptors are commonly expressed in wide variety of normal tissues, it is not well understood why TRAIL kills tumor cells but leaves normal cells unharmed. The prototypic oncogene c-Myc promotes the cell cycle and simultaneously primes activation of the Bcl-2 family controlled mitochondria apoptosis pathway. A striking reflection of the c-Myc-dependent apoptotic sensitization is the dramatic c-Myc-induced vulnerability of cells to TRAIL and other death receptor ligands. Here we summarize the recent findings regarding the death mechanisms of TRAIL/TRAIL receptor system and the connection of c-Myc to the mitochondrial apoptosis pathway, focusing on our work that couples c-Myc via Bak to the TRAIL death receptor pathway. Finally, we present a mitochondria-priming model to explain how c-Myc-Bak interaction amplifies the TRAIL-induced caspase 8-Bid pathway to induce full-blown apoptosis. We discuss the implications of these findings for understanding the selective cytotoxicity of TRAIL and for the therapeutic exploitation of the death receptor pathway.",
    author = "Anni Nieminen and Johanna Partanen and Juha Klefstr{\"o}m",
    year = "2007",
    language = "English",
    volume = "6",
    pages = "2464--2472",
    journal = "Cell Cycle",
    issn = "1538-4101",
    publisher = "Landes Bioscience",
    number = "20",

    }

    c-Myc blazing a trail of death : coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc. / Nieminen, Anni; Partanen, Johanna; Klefström, Juha.

    In: Cell Cycle, Vol. 6, No. 20, 2007, p. 2464-2472.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - c-Myc blazing a trail of death

    T2 - coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc

    AU - Nieminen, Anni

    AU - Partanen, Johanna

    AU - Klefström, Juha

    PY - 2007

    Y1 - 2007

    N2 - TRAIL ligand induces selectively apoptosis in tumor cells by binding to two death receptors (DR4 and DR5) and holds promise as a potential therapeutic agent against cancer. While it has been known for long time that TRAIL receptors are commonly expressed in wide variety of normal tissues, it is not well understood why TRAIL kills tumor cells but leaves normal cells unharmed. The prototypic oncogene c-Myc promotes the cell cycle and simultaneously primes activation of the Bcl-2 family controlled mitochondria apoptosis pathway. A striking reflection of the c-Myc-dependent apoptotic sensitization is the dramatic c-Myc-induced vulnerability of cells to TRAIL and other death receptor ligands. Here we summarize the recent findings regarding the death mechanisms of TRAIL/TRAIL receptor system and the connection of c-Myc to the mitochondrial apoptosis pathway, focusing on our work that couples c-Myc via Bak to the TRAIL death receptor pathway. Finally, we present a mitochondria-priming model to explain how c-Myc-Bak interaction amplifies the TRAIL-induced caspase 8-Bid pathway to induce full-blown apoptosis. We discuss the implications of these findings for understanding the selective cytotoxicity of TRAIL and for the therapeutic exploitation of the death receptor pathway.

    AB - TRAIL ligand induces selectively apoptosis in tumor cells by binding to two death receptors (DR4 and DR5) and holds promise as a potential therapeutic agent against cancer. While it has been known for long time that TRAIL receptors are commonly expressed in wide variety of normal tissues, it is not well understood why TRAIL kills tumor cells but leaves normal cells unharmed. The prototypic oncogene c-Myc promotes the cell cycle and simultaneously primes activation of the Bcl-2 family controlled mitochondria apoptosis pathway. A striking reflection of the c-Myc-dependent apoptotic sensitization is the dramatic c-Myc-induced vulnerability of cells to TRAIL and other death receptor ligands. Here we summarize the recent findings regarding the death mechanisms of TRAIL/TRAIL receptor system and the connection of c-Myc to the mitochondrial apoptosis pathway, focusing on our work that couples c-Myc via Bak to the TRAIL death receptor pathway. Finally, we present a mitochondria-priming model to explain how c-Myc-Bak interaction amplifies the TRAIL-induced caspase 8-Bid pathway to induce full-blown apoptosis. We discuss the implications of these findings for understanding the selective cytotoxicity of TRAIL and for the therapeutic exploitation of the death receptor pathway.

    M3 - Article

    VL - 6

    SP - 2464

    EP - 2472

    JO - Cell Cycle

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    ER -