Department of Pathophysiology, Shanghai Univeristies E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, China.
Arch Immunol Ther Exp (Warsz). 2012 Oct;60(5):361-72. doi: 10.1007/s00005-012-0188-8. Epub 2012 Aug 24.
Protein kinase C-delta (PKCδ), a member of the lipid-regulated serine/threonine PKC family, has been implicated in a wide range of important cellular processes. In the past decade, the critical role of PKCδ in the regulation of both intrinsic and extrinsic apoptosis pathways has been widely explored. In most cases, over-expression or activation of PKCδ results in the induction of apoptosis. The phosphorylations and multiple cell organelle translocations of PKCδ initiate apoptosis by targeting multiple downstream effectors. During apoptosis, PKCδ is proteolytically cleaved by caspase-3 to generate a constitutively activated catalytic fragment, which amplifies apoptosis cascades in nucleus and mitochondria. However, PKCδ also exerts its anti-apoptotic and pro-survival roles in some cases. Therefore, the complicated role of PKCδ in apoptosis appears to be stimulus and cell type dependent. This review is mainly focused on how PKCδ gets activated in diverse ways in response to apoptotic signals and how PKCδ targets different downstream regulators to sponsor or restrain apoptosis induction.
蛋白激酶 C-δ（PKCδ）是脂调节丝氨酸/苏氨酸 PKC 家族的成员，它与广泛的重要细胞过程有关。在过去的十年中，PKCδ 在调节内在和外在细胞凋亡途径中的关键作用得到了广泛的探索。在大多数情况下，PKCδ 的过度表达或激活会导致细胞凋亡。PKCδ 通过靶向多个下游效应物的磷酸化和多个细胞细胞器易位来启动细胞凋亡。在细胞凋亡过程中，PKCδ 被 caspase-3 蛋白水解切割，产生一个组成性激活的催化片段，该片段放大细胞核和线粒体中的细胞凋亡级联反应。然而，在某些情况下，PKCδ 也发挥其抗凋亡和促生存作用。因此，PKCδ 在细胞凋亡中的复杂作用似乎取决于刺激和细胞类型。本综述主要集中于 PKCδ 如何以不同的方式响应凋亡信号而被激活，以及 PKCδ 如何靶向不同的下游调节因子来促进或抑制细胞凋亡的诱导。
