Cellular FLICE-inhibitory protein (c-FLIP) signalling: A key regulator of receptor-mediated apoptosis in physiologic context and in cancer
Cellular FLICE-inhibitory protein (c-FLIP) signalling: A key regulator of receptor-mediated apoptosis in physiologic context and in cancer
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DOI：
10.1016/j.biocel.2009.11.015
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发表时间：
2010-02-01
影响因子：
4
通讯作者：
Mezzanzanica, Delia
中科院分区：
文献类型：
--
作者：
Bagnoli, Marina;Canevari, Silvana;Mezzanzanica, Delia
细胞FLICE-inhibitory protein （c-FLIP）是一种催化失活的procaspase-8/10同源物，与死亡受体下游的信号复合物相关，负性干扰凋亡信号传导。已经确定了三种c-FLIP剪接变体：c-FLIP(L), c-FLIP(S)和c-FLIP(R)，这三种变体在生理和病理背景下都作为凋亡抑制剂参与调节caspase-8/10活性。此外，根据caspase-8与c-FLIP(L)的比值，细胞类型特异性促凋亡作用也被描述为长异构体。本文综述了c-FLIP蛋白的功能和调控方面的研究进展，重点介绍了c-FLIP(L)在癌症中的失调控表达。本文讨论了c-FLIP(L)作为肿瘤中抗凋亡促生存因子的作用，以及该分子作为一种可能的替代治疗靶点的潜在效用。2009爱思唯尔有限公司版权所有。
Cellular FLICE-inhibitory protein (c-FLIP) is a catalytically inactive procaspase-8/10 homologue that associates with the signalling complex downstream of death-receptors negatively interfering with apoptotic signalling. Three c-FLIP splice variants have been identified: c-FLIP(L), c-FLIP(S) and c-FLIP(R), with all three functioning as apoptosis inhibitors involved in modulation of caspase-8/10 activity in both physiologic and pathologic contexts. Furthermore, a cell-type specific pro-apoptotic role, depending on caspase-8 to c-FLIP(L) ratio, has also been described for the long isoform. The present review summarizes recent findings concerning c-FLIP proteins' function and regulation, with a main focus on the c-FLIP(L) deregulated expression in cancer. The role of c-FLIP(L) as anti-apoptotic pro-survival factor in tumors and the potential utility of this molecule as a possible alternative therapeutic target are discussed. (C) 2009 Elsevier Ltd. All rights reserved.