Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB.
Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB.
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DOI：
10.1371/journal.pone.0089485
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Emiliani C
中科院分区：
文献类型：
--
作者：
Urbanelli L;Magini A;Ercolani L;Sagini K;Polchi A;Tancini B;Brozzi A;Armeni T;Principato G;Emiliani C
在许多细胞模型中，H-RasV12癌基因的表达被描述为诱导增殖停滞和过早衰老。许多研究表明衰老与溶酶体酶的改变有关，例如溶酶体β-半乳糖苷酶是检测培养细胞衰老的最广泛使用的生物标志物，我们先前报道H-RasV12上调人成纤维细胞中溶酶体糖水解酶的活性。在这里，我们研究了溶酶体糖水解酶β-己糖氨酸酶上调人成纤维细胞表达固有活性H-RasV12的分子机制。我们证明了H-RAS的激活通过依赖于转录因子EB(TFEB)活性的Raf/细胞外信号调节的蛋白激酶依赖途径来增加β-己糖氨酸酶的表达和分泌。由于TFEB在溶酶体系统的生物发生和功能调节中起着关键作用，我们的结果提示这可能是在癌基因诱导的衰老过程中提高溶酶体酶活性的一般机制。
The expression of constitutively active H-RasV12 oncogene has been described to induce proliferative arrest and premature senescence in many cell models. There are a number of studies indicating an association between senescence and lysosomal enzyme alterations, e.g. lysosomal β-galactosidase is the most widely used biomarker to detect senescence in cultured cells and we previously reported that H-RasV12 up-regulates lysosomal glycohydrolases enzymatic activity in human fibroblasts. Here we investigated the molecular mechanisms underlying lysosomal glycohydrolase β-hexosaminidase up-regulation in human fibroblasts expressing the constitutively active H-RasV12. We demonstrated that H-Ras activation increases β-hexosaminidase expression and secretion by a Raf/extracellular signal-regulated protein kinase dependent pathway, through a mechanism that relies on the activity of the transcription factor EB (TFEB). Because of the pivotal role of TFEB in the regulation of lysosomal system biogenesis and function, our results suggest that this could be a general mechanism to enhance lysosomal enzymes activity during oncogene-induced senescence.
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影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
3.7
作者：
Armeni T;Ercolani L;Urbanelli L;Magini A;Magherini F;Pugnaloni A;Piva F;Modesti A;Emiliani C;Principato G
通讯作者：
Principato G
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
通过基于 DIGE 的蛋白质组学分析分析与前列腺癌淋巴结转移相关的蛋白质标记
影响因子：
4.4
作者：
Pang, Jun;Liu, Wei-Peng;Gao, Xin
通讯作者：
Gao, Xin
DOI：
10.1016/s0304-4165(96)00116-x
发表时间：
1997-04-17
影响因子：
3
作者：
Martino, S;Emiliani, C;Orlacchio, A
通讯作者：
Orlacchio, A