Elongin C is a mediator of Notch4 activity in human renal tubule cells.
Elongin C is a mediator of Notch4 activity in human renal tubule cells.
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弹蛋白C是人肾小管细胞中Notch4活性的介体。
DOI：
10.1016/j.bbapap.2011.09.010
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Powell DW
中科院分区：
文献类型：
--
作者：
Cummins TD;Mendenhall MD;Lowry MN;Korte EA;Barati MT;Khundmiri SJ;Salyer SA;Klein JB;Powell DW
Notch蛋白（Notch 1-4）是跨膜细胞表面受体家族，当通过与相邻细胞上的细胞表面配体相互作用而被激活时，所述跨膜细胞表面受体被转化为转录调节因子。配体结合刺激跨膜结构域的蛋白水解裂解，释放易位到细胞核并影响转录的活性细胞内结构域（ICD）。在转运过程中，ICD可能与调节表达和转录活性的调节蛋白相互作用。我们已经发现Notch 4 ICD表达在糖尿病小鼠和人类的纤维化肾脏的小管细胞中增强，并且鉴定了可能与正常和病理功能相关的Notch 4 ICD相互作用蛋白。使用蛋白质组学技术，几个组成部分的延伸蛋白C复合物被确定为候选Notch 4 ICD相互作用。延伸蛋白C复合物可以作为能够调节特定蛋白质底物的蛋白酶体降解的泛素连接酶起作用。我们的研究表明，在人肾小管HK 11细胞中，异位的延伸蛋白C表达刺激Notch 4 ICD降解并抑制其转录活性。阻断MG 132介导的延伸蛋白C降解表明Notch 4 ICD的泛素介导的延伸蛋白C调节的潜力。Notch 4 ICD和Elongin C的功能相互作用为Notch信号在上皮细胞生物学和疾病中的调节提供了新的见解。
Notch proteins (Notch 1–4) are a family of trans-membrane cell surface receptors that are converted into transcriptional regulators when activated by interactions with cell surface ligands on adjacent cells. Ligand-binding stimulates proteolytic cleavage of the trans-membrane domain, releasing an active intracellular domain (ICD) that translocates to the nucleus and impacts transcription. In transit, the ICD may interact with regulatory proteins that modulate the expression and transcriptional activity. We have found that Notch4ICD expression is enhanced in the tubule cells of fibrotic kidneys from diabetic mice and humans and identified Notch4ICD interacting proteins that could be pertinent to normal and pathological functions. Using proteomic techniques, several components of the Elongin C complex were identified as candidate Notch4ICD interactors. Elongin C complexes can function as ubiquitin ligases capable of regulating proteasomal degradation of specific protein substrates. Our studies indicate that ectopic Elongin C expression stimulates Notch4ICD degradation and inhibits its transcriptional activity in human kidney tubule HK11 cells. Blocking Elongin C mediated degradation by MG132 indicates the potential for ubiquitin-mediated Elongin C regulation of Notch4ICD. Functional interaction of Notch4ICD and Elongin C provides novel insight into regulation of Notch signaling in epithelial cell biology and disease.
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DOI：
10.1073/pnas.96.22.12436
发表时间：
1999-10-26
影响因子：
11.1
作者：
Iwai, K;Yamanaka, K;Pause, A
通讯作者：
Pause, A
影响因子：
6.7
作者：
Cai, Qi-Liang;Knight, Jason S;Verma, Suhbash C;Zald, Philip;Robertson, Erle S
通讯作者：
Robertson, Erle S
影响因子：
4.8
作者：
Heuzé, ML;Guibal, FC;Lutz, PG
通讯作者：
Lutz, PG
影响因子：
5.3
作者：
Gerber, M;Eissenberg, JC;Shilatifard, A
通讯作者：
Shilatifard, A
影响因子：
4.8
作者：
Luo, Kun;Ehrlich, Elana;Yu, Xiao-Fang
通讯作者：
Yu, Xiao-Fang