The Pirh2-keratin 8/18 interaction modulates the cellular distribution of mitochondria and UV-induced apoptosis
The Pirh2-keratin 8/18 interaction modulates the cellular distribution of mitochondria and UV-induced apoptosis
复制标题
Pirh2-角蛋白 8/18 相互作用调节线粒体的细胞分布和紫外线诱导的细胞凋亡
DOI：
10.1038/cdd.2009.12
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发表时间：
2009-06-01
影响因子：
12.4
通讯作者：
Wu, M.
中科院分区：
文献类型：
--
作者：
Duan, S.;Yao, Z.;Wu, M.
中间纤维（IF）在高等真核细胞中提供重要的结构支持。越来越多的证据表明，IFs还通过与各种非结构蛋白的动态相互作用参与各种细胞活动，包括应激反应、细胞生长、细胞死亡和细胞迁移。在这里，我们报告的识别Pirh 2，RING-H2型泛素E3连接酶，作为一种新的结合伴侣的细胞质IF蛋白角蛋白8/18（K8/18）。Pirh 2或K8/18的磷酸化影响它们的缔合。虽然没有发现Pirh 2影响K8/18的稳定性，但它在调节K8/18角蛋白丝网络的组织中显示出意想不到的作用。通过UV照射或用Pirh 2或K18敲低破坏Pirh 2-K8/K18相互作用导致K8/18角蛋白丝聚集。它进一步诱导线粒体重新分布，这一过程可能是通过微管介导的途径。Pirh 2敲除细胞中线粒体的异常定位可能部分地解释了其对UV诱导的细胞凋亡的增加的细胞敏感性，这可能是通过增强促凋亡蛋白如细胞色素c和Smac/DIABLO向胞质溶胶的释放。总的来说，我们的数据揭示了Pirh 2-K8/18复合物在控制线粒体分布中的新作用。Cell Death and Differentiation（2009）16，826-837; doi：10.1038/cdd.2009.12; 2009年3月13日在线发表
Intermediate filaments (IFs) provide crucial structural support in higher eukaryotic cells. Accumulating evidences show that IFs also participate in various cellular activities including stress responses, cell growth, cell death and cell migration through dynamic interactions with various non-structure proteins. Here we report the identification of Pirh2, a RING-H2-type ubiquitin E3 ligase, as a novel binding partner of the cytoplasmic IF proteins keratin 8/18 (K8/18). Phosphorylation of either Pirh2 or K8/18 affects their association. Although Pirh2 was not found to influence the stability of K8/18, it displayed an unexpected role in regulating the organization of the network of K8/18 keratin filaments. Disruption of Pirh2-K8/K18 interaction by either UV irradiation or knockdown with Pirh2 or K18 led to the aggregation of K8/18 keratin filaments. It further induced mitochondrial redistribution, and this process is likely through a microtubule-mediated pathway. The abnormal localization of mitochondria in Pirh2-knockdown cells may partially account for its increased cell sensitivity to UV-induced apoptosis, probably through enhancing the release of pro-apoptotic proteins, such as cytochrome c and Smac/DIABLO to the cytosol. Overall, our data reveal the novel role of the Pirh2-K8/18 complex in governing the distribution of mitochondria. Cell Death and Differentiation (2009) 16, 826-837; doi: 10.1038/cdd.2009.12; published online 13 March 2009