核WWOX/TRAF2开关的解离在低温下导致UV/冷冲击介导的核泡细胞死亡
Szu-Jung Chen1, Cheng-Chang Tsai1, Sing-Ru Lin1
1Institute of Molecular Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
Cell communication and signaling : CCS
|October 17, 2024
概括
具有功能性瘤抑制剂WW域含氧化还原酶 (WWOXf) 的正常细胞在暴露于紫外线和寒冷时经历泡细胞死亡 (BCD). 缺乏WWOX的细胞经历了不同的死亡途径. 温度通过WWOX/TRAF2复合体决定细胞死亡的命运.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 正常细胞表达功能性瘤抑制剂WW域含氧化还原酶 (WWOXf).
- 紫外线照射诱导WWOXf细胞通过核氧化 (NO) 气体积聚而经历泡性细胞死亡 (BCD).
- 缺乏WWOX (WWOXd) 的细胞在紫外线/寒冷冲击后表现出核弹出爆炸死亡 (POD).
研究的目的:
- 在WWOXf细胞中研究BCD和细胞亡之间的形态和生化差异.
- 阐明温度在调节细胞死亡途径中的作用.
主要方法:
- 使用时隔显微镜和全息显微镜可视化WWOXf和WWOXd细胞在UV和/或冷冲击后的不同温度 (4,22,37°C) 的形态变化.
- 活细胞染色评估了氧化 (NO) 生产和流入.
- 酸的吸收和DNA碎片化测量细胞死亡程度.
主要成果:
- 紫外线诱导的流入和NO产生导致WWOXf细胞中的BCD.
- 寒冷冲击抑制了在37°C的紫外线媒介泡,而不是诱导亡.
- WWOXd细胞经历了NO-独立的POD.
- 紫外线/寒冷冲击降低了诸如α-tubulin和β-actin之类的关键蛋白质的调节,并诱导了α-tubulin的转移.
- 紫外线诱导WWOX/TRAF2复合体转移到核中,其中TRAF2抑制了WWOX.
- 寒冷冲击使WWOX/TRAF2复合体脱离,有利于BCD,而37°C的复合体形成则支持了亡.
结论:
- 对温度敏感的WWOX/TRAF2复合体作为一个分子开关.
- 在低温下复合物的解离有利于BCD.
- 综合体在37°C的结合支持紫外线处理的WWOXf细胞的亡.
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