TWEAK affects keratinocyte G2/M growth arrest and induces apoptosis through the translocation of the AIF protein to the nucleus.
TWEAK affects keratinocyte G2/M growth arrest and induces apoptosis through the translocation of the AIF protein to the nucleus.
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DOI：
10.1371/journal.pone.0033609
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tsapis A
中科院分区：
文献类型：
--
作者：
Sabour Alaoui S;Dessirier V;de Araujo E;Alexaki VI;Pelekanou V;Lkhider M;Stathopoulos EN;Castanas E;Bagot M;Bensussan A;Tsapis A
可溶性tnf样细胞凋亡弱诱导剂（TWEAK, TNFSF12）与细胞膜上的成纤维细胞生长因子诱导14受体（FN14, TNFRSF12A）结合，诱导增殖、迁移、分化、血管生成和细胞凋亡等多种生物学反应。以前的报道表明，在细胞质尾部不含死亡结构域的TWEAK通过诱导TNFα分泌来诱导肿瘤细胞系的凋亡。TWEAK诱导人角质形成细胞凋亡。我们的实验清楚地表明，TWEAK不会诱导TNFα或TRAIL蛋白的分泌。特异性抑制剂的使用和procaspase-3切割的缺失表明，角质形成细胞的凋亡遵循caspase-和组织蛋白酶b独立的途径。进一步的研究表明，TWEAK诱导了角质形成细胞线粒体膜电位的降低。共聚焦显微镜显示，TWEAK诱导细胞凋亡诱导因子（apoptosis inducing factor， AIF）从线粒体裂解并易位至细胞核，从而启动caspase非依赖性细胞凋亡。此外，TWEAK诱导FOXO3和GADD45表达，cdc2磷酸化，cdc2和cyclinB1降解，导致细胞生长停滞在G2/M期。最后，我们报道了TWEAK和FN14通常在生理表皮的基底层表达，并且在以炎症成分为特征的良性（牛皮癣）和恶性（鳞状细胞癌）皮肤病理中大大增强。TWEAK可能在皮肤稳态和病理中起重要作用。
The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology.
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DOI：
10.1161/01.atv.0000062883.93715.37
发表时间：
2003-04-01
影响因子：
8.7
作者：
Donohue, PJ;Richards, CM;Winkles, JA
通讯作者：
Winkles, JA
影响因子：
6.5
作者：
Dai, X;Yamasaki, K;Hashimoto, K
通讯作者：
Hashimoto, K
影响因子：
4.4
作者：
Alexaki, Vassilia-Ismini;Notas, George;Castanas, Elias
通讯作者：
Castanas, Elias
影响因子：
3.6
作者：
Kim, Dong-Seok;Lee, Hyun-Kyung;Park, Kyoung-Chan
通讯作者：
Park, Kyoung-Chan
DOI：
10.1016/s0006-291x(02)02670-0
发表时间：
2002-12-06
影响因子：
3.1
作者：
Harada, N;Nakayama, M;Okumura, K
通讯作者：
Okumura, K