WWOX drives UV/cold shock‐induced bubbling cell death whereas without WWOX cells pop out

Bubbling cell death (BCD) is known as release of an enlarging nuclear bubble from the surface of each cell at room temperature or lower post exposure of the cells to UV irradiation and cold shock. BCD concerns the severity of frostbite and UV. However, the molecular mechanism is largely unknown. Here, we determined that UV/cold shock induces tumor suppressor WWOX‐expressing L929S cells to undergo typical BCD. UV energy is rapidly taken up by the nuclear DNA to transmit signals and simultaneous rapid influx of calcium ion, followed by nuclear accumulation of numerous cytosolic and membrane proteins (e.g. p53, WWOX, TRAF2, NOS2, NF‐κB, C1q and Hyal‐2). Subsequently, release of nucleolar content leads to irreversible bubble formation and death without cell shrinkage. BCD is blocked at 37°C in L929S and other WWOX‐positive cells. Notably, transient overexpression of TIAF1 and SH3GLB2 restores BCD in TNF‐sensitive L929S cells at 37°C. In contrast, UV/cold shock‐treated WWOX‐deficient cells undergo shrinkage, then rapid nuclear bubble formation and final whole cell pop‐out, designated pop‐out death (POD). Antiapoptotic TRAF2 binds WWOX and the binding is abolished during BCD, suggesting that the dissociated WWOX is needed in inducing BCD. Support or Funding Information Research was supported by the Ministry of Science and Technology, Taiwan (MOST 105‐2320‐B‐006‐046, 105‐2320‐B‐006‐036,106‐2320‐B‐006‐017, and 106‐2320‐B‐006‐061), the Department of Defense, USA (W81XWH‐08–1‐0682), the National Health Research Institute, Taiwan (NHRI‐EX107‐10734NI) to NS Chang. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .