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TAp63alpha is involved in toll‐like receptor 3 (TLR3) induced apoptosis via death receptors and mitochondria
Author(s) -
Hu Jinyue,
Sun Ruili,
Zhang Yu,
Liu Bei,
Jin Miao,
Zhang Weijia,
Deng Minjie,
Liu Xueting,
Li Guancheng,
Li Yuehui,
Zhuo Guohua,
Xie Pingli,
Duan Zhaojun
Publication year - 2011
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.25.1_supplement.952.1
Subject(s) - tlr3 , microbiology and biotechnology , apoptosis , signal transduction , receptor , mitochondrion , programmed cell death , priming (agriculture) , biology , toll like receptor , chemistry , innate immune system , biochemistry , botany , germination
TLR3 is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing virus double strain RNA. Recently, it has been reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that Poly I:C induced TLR3 dependent cell death in endothelial cells. Poly I:C treatment activated both caspase 8 and 9, indicating that TLR3 triggered the signaling of both extrinsic and intrinsic pathways. Poly I:C treatment up‐regulated TRAIL and DR4/5, resulting in the initiating of extrinsic pathway. Meanwhile, Poly I:C down‐regulated Bcl‐2, up‐regulated Noxa, leading to the priming of intrinsic pathway. A p53 related protein, TAp63alpha was induced by TLR3 activation and contributed to the activation of both intrinsic and extrinsic apoptosis pathways. The cells deficient in p63 gene expression by RNA interference and the cells over expressed DNp63alpha, a dominant negative variant of TAp63alpha, survived TLR3 activation. Taken together, TAp63alpha as a crucial regulator functions downstream of TLR3 in inducing cell death via both death receptors and mitochondria.