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WWOX/WOX1 is essential in UV irradiation/frostbite‐induced membrane bubbling
Author(s) -
Chen Szu-Jung,
Huang Shenq-Shyang,
Chang Nan-Shan
Publication year - 2012
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.26.1_supplement.798.8
Subject(s) - wwox , nucleus , chemistry , microbiology and biotechnology , apoptosis , cytosol , programmed cell death , phosphatidylserine , fragmentation (computing) , biophysics , membrane , suppressor , biology , biochemistry , gene , phospholipid , enzyme , ecology
Overexposure to extreme cold, along with incidental UV irradiation, causes tissue damage and death ‐ the so called frostbite. Time lapse imaging analysis showed that post UV irradiation, COS7 fibroblasts undergo tiny, fluctuating membrane blebbing and then explode with a big bubble from the nucleus. Cold shock at 4oC significantly enhances the UV‐induced bubbling event. UV energy appears to be absorbed by the nucleus, so as to punch off a tiny nuclear pore that allows pressure release from the nucleus and subsequent plasma membrane exploding, as evidenced by using ECFP‐tagged nuclear protein. Unlike apoptosis, these COS7 cells exhibit little or no DNA fragmentation, cell shrinkage and phosphatidylserine expsoure. Blebbistatin, a blebs formation inhibitor, failed to prevent cells from bubbling up. Intriguingly, bubbling of Wwox gene knock out MEF (Wwox−/−) cells are significantly reduced, suggesting a crucial role of tumor suppressor WWOX/WOX1 in the bubbling event. Mechanistically, WWOX/WOX1 dissociates from TRAF2 for mitochondrial and nuclear relocation that contributes, in part, bubbling and death. [Supported by NSC and NHRI, Taiwan, and DoD, USA]