Nuclear localization of c-FLIP-L and its regulation of AP-1 activity.
Nuclear localization of c-FLIP-L and its regulation of AP-1 activity.
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DOI：
10.1016/j.biocel.2009.02.008
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发表时间：
2009-08
期刊：
影响因子：
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通讯作者：
Jing Zhang;Yunzi Chen;Qilai Huang;Wei Cheng;Yuan-Xi Kang;L. Shu;Wu Yin;Z. Hua
中科院分区：
文献类型：
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作者：
Jing Zhang;Yunzi Chen;Qilai Huang;Wei Cheng;Yuan-Xi Kang;L. Shu;Wu Yin;Z. Hua
细胞Flice样抑制蛋白(c-flip-L)与半胱氨酸天冬氨酸氨基转移酶-8(caspase-8)结构相似，可通过与椎间盘FADD结合，阻断Fas或其他死亡受体(DR)介导的细胞凋亡。最近的研究表明c-flip-L在T细胞增殖中的作用，但这一过程的确切机制仍有待阐明。在本报告中，我们首次发现c-flip-L既存在于细胞质中，也存在于细胞核中，但在细胞核中分布更为丰富。推测的NLS信号位于caspase样域的p12区域。此外，c-FLIP的胞膜转运依赖于细胞的凋亡刺激，而增殖刺激则使其迅速转运至胞核。为了深入了解c-flip-L在细胞核中的可能功能，我们发现c-flip-L可以激活AP-1的转录活性，而不是MAPK的激活。总之，我们的发现描述了c-flip-L在AP-1激活和细胞增殖中的一个新功能。
Cellular FLICE-like inhibitory protein (c-FLIP-L), similar in structure to caspase-8, is capable of blocking Fas- or other death receptors (DR)-mediated apoptosis through association with FADD in the DISC. Recent studies have implicated the function of c-FLIP-L in T-cell proliferation, but the exact mechanism underlying this process remains to be elucidated. In this report, we showed for the first time that c-FLIP-L was present in both the cytoplasm and nucleus of cells, but was more abundantly distributed in the nucleus. The putative NLS signal locates within the p12 region of caspase-like domain. Furthermore, c-FLIP's export to cytoplasm membrane was dependent on apoptotic stimulation, while it rapidly translocated to the nucleus in response to proliferative stimuli. To gain insights into the possible function of c-FLIP-L in the nucleus, we found c-FLIP-L could activate the AP-1 transcriptional activity independent of MAPK activation. In sum, our findings describe a novel function of c-FLIP-L involved in AP-1 activation and cell proliferation.