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    Home > Biochemistry News > Biotechnology News > Two new breakthroughs in Nature's anti-cancer: new epigenetic target-NSD3

    Two new breakthroughs in Nature's anti-cancer: new epigenetic target-NSD3

    • Last Update: 2021-03-26
    • Source: Internet
    • Author: User
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    In the human body, gene expression is dynamic, but it is also strictly regulated.


    Adding various chemical markers to DNA and DNA-related proteins is a way to control gene expression.


    In the cell, DNA wraps around protein clusters called histones to form the basic structural unit of chromatin—nucleosomes.


    Enzymes that add or remove epigenetic modifications are often overexpressed or mutated in cancer, which suggests that they play a role in cancer development and maintenance.


    NSD3 is a member of the nuclear receptor-binding SET domain protein (NSD) family of histone methyltransferases, which also includes NSD1 and NSD2.


    Studies have found that in human tumors, NSD3 becomes dysregulated.


    Using genome analysis techniques, scientists have discovered that oncogenic NSD3 catalyzes the dimethylation of H3K36 in the protein coding region of oncogenes, leading to higher expression rates of these genes.


    In a related paper published in December 2020, Professor Gozani and his collaborators used cryo-electron microscopy to reveal the different structural features of normal NSD3 and oncogenic mutant NSD3 bound to nucleosomes.


    Structural analysis also revealed how NSD3 oncogenic mutations lead to the formation of new hydrogen bonds with histones, explaining why the mutants have enhanced catalytic activity.


    It is worth noting that a study published in Nature Chemical Biology last year described small molecules that covalently inhibit the function of NSD1 methyltransferase, which is a proof of concept for the idea that "selective targeting of NSD is feasible" [3].


    Nature's opinion article on these new findings believes that inhibiting NSD3 may become a new cancer targeted therapy strategy.


    Reference materials:

    [1] Gang Yuan et al.


    [2] Wanqiu Li et al.


    [3] Huang Huang et al.


    [4] An epigenetic tipping point in cancer comes under the microscope (Source: Nature)

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