JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins.
JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins.
复制标题
DOI：
10.1016/j.celrep.2017.10.067
复制
发表时间：
2017-11-14
期刊：
影响因子：
8.8
通讯作者：
Davis RJ
中科院分区：
文献类型：
--
作者：
Girnius N;Davis RJ
发育形态发生、组织损伤和致癌转化可引起上皮细胞的脱落。这些细胞被一种特殊形式的凋亡（失巢凋亡）所消除。虽然已经研究了导致这种形式的细胞死亡的过程，但其潜在机制仍不清楚。在这里，我们测试的cJUN氨基末端激酶（JNK）信号通路的作用，使用小鼠模型与化合物JNK缺陷的乳腺和肾上皮细胞。这些研究表明，JNK是体外和体内有效失巢凋亡所必需的。此外，JNK促进的失巢凋亡需要BCL 2蛋白家族的促凋亡成员。我们发现JNK通过增加BIM表达和磷酸化BMF导致脱落上皮细胞死亡，通过巴克/BAX依赖性凋亡途径起作用。发育形态发生、组织损伤和致癌转化可引起上皮细胞脱离。这些细胞被称为失巢凋亡的专门形式消除。Girnius和Davis表明失巢凋亡由cJUN NH 2-末端激酶（JNK）介导，其增加BIM表达并磷酸化BMF以参与巴克/BAX依赖性凋亡。
Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK-deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that JNK acts through a BAK/BAX-dependent apoptotic pathway by increasing BIM expression and phosphorylating BMF leading to death of detached epithelial cells. Developmental morphogenesis, tissue injury, and oncogenic transformation can cause epithelial cell detachment. These cells are eliminated by a specialized form of apoptosis termed anoikis. Girnius and Davis show that anoikis is mediated by the cJUN NH2-terminal kinase (JNK), which increases BIM expression and phosphorylates BMF to engage BAK/BAX-dependent apoptosis.
登录
查看更多内容
Jun-N末端激酶在Anoikis中的作用； Bcl-2和CRMA抑制。
影响因子：
7.8
作者：
Frisch, SM;Vuori, K;Kelaita, D;Sicks, S
通讯作者：
Sicks, S
Jun-NH2-末端激酶激活与上皮细胞分离后凋亡的诱导之间缺乏相关性。
影响因子：
7.8
作者：
Khwaja, A;Downward, J
通讯作者：
Downward, J
影响因子：
2.7
作者：
Adachi-Yamada, T;O'Connor, MB
通讯作者：
O'Connor, MB
影响因子：
56.9
作者：
Bouillet, P;Metcalf, D;Strasser, A
通讯作者：
Strasser, A
影响因子：
7.2
作者：
Igaki, Tatsushi
通讯作者：
Igaki, Tatsushi