The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin.
The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin.
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Batten 病基因 CLN3 赋予对衣霉素诱导的内质网应激的抵抗力。
DOI：
10.1016/j.bbrc.2014.03.120
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发表时间：
2014
影响因子：
3.1
通讯作者：
Jianyuan Luo
中科院分区：
文献类型：
--
作者：
Dan Wu;Jing Liu;Baiyan Wu;Bo Tu;Wei;Jianyuan Luo
CLN3基因突变导致幼年神经元蜡样脂褐素沉着症(JNCL或Batten病)，这是一种早期起病的神经退行性疾病，其特征是蜡样脂褐素在溶酶体内积聚。CLN3蛋白的功能尚不清楚，推测与内质网应激有关。为了探讨CLN3在内质网应激信号通路中的作用，我们检测了内质网应激诱导剂衣霉素(TM)处理后，转染正常和突变CLN3的细胞的增殖和凋亡情况。我们发现，CLN3的过度表达足以增强对内质网胁迫的抗性。野生型CLN3对TM诱导的细胞凋亡和促进细胞增殖具有保护作用。野生型CLN3的过表达增强了ER伴侣蛋白葡萄糖调节蛋白78(GRP78)的表达，降低了促凋亡蛋白CCAAT/增强子结合蛋白同源蛋白(CHOP)的表达。相反，过表达突变的CLN3或下调CLN3的siRNA则产生相反的效果。综上所述，我们的数据表明，细胞中CLN3功能的缺乏导致了对内质网应激反应的管理失败，这可能是JNCL导致神经元退化的关键缺陷。
Mutations inCLN3gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function ofCLN3in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutantCLN3after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression ofCLN3was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.
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影响因子：
3.5
作者：
Wei, Hui;Kim, Sung-Jo;Mukherjee, Anil B.
通讯作者：
Mukherjee, Anil B.
影响因子：
3.5
作者：
Zhang, ZJ;Lee, YC;Mukherjee, AB
通讯作者：
Mukherjee, AB
影响因子：
3.8
作者：
Puranam, KL;Guo, WX;Boustany, RM
通讯作者：
Boustany, RM
CLN3 基因的跨物种同源性。
影响因子：
1.4
作者：
Taschner,PE;deVos,N;Breuning,MH
通讯作者：
Breuning,MH
DOI：
10.1016/j.bbrc.2004.03.146
发表时间：
2004-05-14
影响因子：
3.1
作者：
Rakheja, D;Narayan, SB;Bennett, MJ
通讯作者：
Bennett, MJ