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The promoting role of hnRNPK‐DDX3 interaction in the apoptosis upon DNA damage
Author(s) -
Chen ChiaoChe,
Yang JenHao,
Lin ChaoHsiung
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb35
Subject(s) - dna damage , apoptosis , microbiology and biotechnology , cancer research , dna , chemistry , heterogeneous nuclear ribonucleoprotein , biology , ribonucleoprotein , biochemistry , gene , rna
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA binding protein that participates in multiple cell functions due to its functional domains. In addition, some of its post‐translational modifications (PTMs) are critical for functions of hnRNPK. Importance of hnRNPK in cancers has been implied by its strong correlation with cancer transformation, progression and migration, but the mechanism how hnRNPK promotes cancer remains ambiguous. Our previous study reported that arginine methylation of hnRNPK negatively regulates U2OS cell apoptosis upon DNA damage. Recently, we showed that DDX3 helicase is a molecular partner of hnRNPK and may be involved in the hnRNPK‐mediated apoptosis upon DNA damage. In this study, we further investigated the role of DDX3 activity in the apoptosis regulation of U2OS cells using a DDX3 inhibitor. Interestingly, this inhibitor not only increased hnRNPK‐mediated apoptosis upon DNA damage but also elevated hnRNPK‐DDX3 interaction during early DNA damage. These results suggests that hnRNK‐DDX3 interaction is important for apoptosis induction by DNA damage. On the other hand, DDX3 has been shown to enhance p53 stabilization during DNA damage. We thus measured the protein level of p53 during treatment of DDX3 inhibitor but found that such treatment decreased both p53 and p21, implying that hnRNK‐DDX3 interaction promotes DNA damage‐induced apoptosis in a p53‐independent manner. In summary, our results suggests that the hnRNPK‐DDX3 interaction is critical for apoptotic regulation upon DNA damage. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .