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UV irradiation/cold shock‐induced NOS2 expression for causing nuclear bubbling is WWOX and p53 dependent (1010.11)
Author(s) -
Chang NanShan,
Chen SzuJung,
Lin PeiWen
Publication year - 2014
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.28.1_supplement.1010.11
Subject(s) - wwox , apoptosis , programmed cell death , cytosol , microbiology and biotechnology , nitric oxide , cancer research , cell , chemistry , biology , suppressor , biochemistry , gene , organic chemistry , enzyme
When a cell receives UV irradiation and cold shock, an untypical apoptosis occurs rapidly in less than 5‐20 min. We determined here that the UV energy activates cytosolic NOS2 (Nitric oxide synthase 2) for generating nitric oxide (NO)‐containing gas, which causes nuclear pore enlargement and a single large‐size bubble formation, as determined by electron microscopy (thus designated bubbling). Unlike typical apoptosis, no DNA fragmentation, nuclear condensation, membrane blebbing, and flip over of phosphatidylserine (PS) on cell membrane was observed. UV irradiation activated tumor suppressor p53 with phosphorylation at Ser46 and WWOX at Tyr33. Intriguingly, cold shock, but not UV, activates antiapoptotic TRAF2 (TNF‐α receptor‐associated factor 2) and downstream NFκB (nuclear factor κB). TRAF2 is abundant in the normal skin, and is significantly decreased in frostbitten skin tissues. In contrast, the expression of tumor suppressor WWOX is greatly upregulated in frostbitten skin. Mechanistically, UV/cold shock induced WWOX release from the WWOX/TRAF2 complex in 30 minutes, and the released WWOX bound p53 for relocating to the nucleus and caused cell death. Both dominant negative p53 and WWOX abolished the effect of UV/cold shock. Also, the UV/cold shock effect was blocked in Wwox‐/‐ MEF cells and in cells transiently overexpressed with TRAF2. Taken together, UV energy activates cellular NOS2 to generate nitric oxide‐containing gas in the nucleus, and causes cell damage in a WWOX/p53‐dependent manner. (Research supported by NSC and NHRI, Taiwan, and DoD, USA) Grant Funding Source : national science council; national health research institute