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腾讯登录Cancer Cell：去泛素化酶调节肝炎、纤维化和癌变
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<p style="text-align: left;" align="center">6月12日，<em>Cancer Cell</em>杂志报道了去泛素化酶，圆柱瘤病（CYLD）肿瘤抑制因子的失活可引发肝细胞的凋亡、炎症、纤维化和癌症。圆柱瘤病（CYLD）肿瘤抑制因子通过去泛素化上游因子，抑制NFκB和有丝分裂原活化蛋白激酶（MAPK）活化途径。</p>
<p style="text-align: left;" align="center"><!--more--></p>
本研究显示，肝特异性阻断CYLD通过自发的或慢性激活TGF-β活化激酶1（TAK1）和c-Jun N末端激酶（JNK）触发了肝门静脉周边区域肝细胞的死亡。随后，肝星形细胞和Kupper细胞活化，进而促进进行性肝纤维化、炎症、肿瘤坏死因子（TNF）产生，以及肝细胞凋亡朝向中央静脉的扩散。在晚些阶段，补偿性增殖导致癌性中心的产生。这些癌性中心特征性地重新表达癌胚肝细胞及干细胞特异性基因。
这些结果证实，CYLD在肝脏作为一种重要肝细胞稳态调节子，通过预防TAK1和JNK不受控的激活，保护着细胞免受自发凋亡之害。
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<img src="http://www.bioon.com/biology/UploadFiles/201206/2012061219085170.jpg" alt="" width="113" height="149" border="0" hspace="0" />
<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://dx.doi.org/10.1016/j.ccr.2012.04.026" target="_blank">10.1016/j.cell.2011.10.017</a>
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<br/><strong>Inactivation of the Deubiquitinase CYLD in Hepatocytes Causes Apoptosis, Inflammation, Fibrosis, and Cancer</strong><br/>
Kostas Nikolaou, Ageliki Tsagaratou, Christina Eftychi, George Kollias, George Mosialos, Iannis Talianidis
The tumor suppressor cylindromatosis (CYLD) inhibits the NFκB and mitogen-activated protein kinase (MAPK) activation pathways by deubiquitinating upstream regulatory factors. Here we show that liver-specific disruption of CYLD triggers hepatocyte cell death in the periportal area via spontaneous and chronic activation of TGF-β activated kinase 1 (TAK1) and c-Jun N-terminal kinase (JNK). This is followed by hepatic stellate cell and Kupffer cell activation, which promotes progressive fibrosis, inflammation, tumor necrosis factor (TNF) production, and expansion of hepatocyte apoptosis toward the central veins. At later stages, compensatory proliferation results in the development of cancer foci featuring re-expression of oncofetal hepatic and stem cell-specific genes. The results demonstrate that, in the liver, CYLD acts as an important regulator of hepatocyte homeostasis, protecting cells from spontaneous apoptosis by preventing uncontrolled TAK1 and JNK activation.
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<p style="text-align: left;" align="center">6月12日，<em>Cancer Cell</em>杂志报道了去泛素化酶，圆柱瘤病（CYLD）肿瘤抑制因子的失活可引发肝细胞的凋亡、炎症、纤维化和癌症。圆柱瘤病（CYLD）肿瘤抑制因子通过去泛素化上游因子，抑制NFκB和有丝分裂原活化蛋白激酶（MAPK）活化途径。</p>
<p style="text-align: left;" align="center"><!--more--></p>
本研究显示，肝特异性阻断CYLD通过自发的或慢性激活TGF-β活化激酶1（TAK1）和c-Jun N末端激酶（JNK）触发了肝门静脉周边区域肝细胞的死亡。随后，肝星形细胞和Kupper细胞活化，进而促进进行性肝纤维化、炎症、肿瘤坏死因子（TNF）产生，以及肝细胞凋亡朝向中央静脉的扩散。在晚些阶段，补偿性增殖导致癌性中心的产生。这些癌性中心特征性地重新表达癌胚肝细胞及干细胞特异性基因。
这些结果证实，CYLD在肝脏作为一种重要肝细胞稳态调节子，通过预防TAK1和JNK不受控的激活，保护着细胞免受自发凋亡之害。
<div id="ztload">
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012061219085170.jpg" alt="" width="113" height="149" border="0" hspace="0" />
<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://dx.doi.org/10.1016/j.ccr.2012.04.026" target="_blank">10.1016/j.cell.2011.10.017</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Inactivation of the Deubiquitinase CYLD in Hepatocytes Causes Apoptosis, Inflammation, Fibrosis, and Cancer</strong><br/>
Kostas Nikolaou, Ageliki Tsagaratou, Christina Eftychi, George Kollias, George Mosialos, Iannis Talianidis
The tumor suppressor cylindromatosis (CYLD) inhibits the NFκB and mitogen-activated protein kinase (MAPK) activation pathways by deubiquitinating upstream regulatory factors. Here we show that liver-specific disruption of CYLD triggers hepatocyte cell death in the periportal area via spontaneous and chronic activation of TGF-β activated kinase 1 (TAK1) and c-Jun N-terminal kinase (JNK). This is followed by hepatic stellate cell and Kupffer cell activation, which promotes progressive fibrosis, inflammation, tumor necrosis factor (TNF) production, and expansion of hepatocyte apoptosis toward the central veins. At later stages, compensatory proliferation results in the development of cancer foci featuring re-expression of oncofetal hepatic and stem cell-specific genes. The results demonstrate that, in the liver, CYLD acts as an important regulator of hepatocyte homeostasis, protecting cells from spontaneous apoptosis by preventing uncontrolled TAK1 and JNK activation.
</div>
</div>
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