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腾讯登录Sci. Signal：核仁定位netrin-1亚型增强肿瘤细胞增殖
| 导读 | Netrin-1 是一种分泌蛋白，能促进中枢神经系统的轴束生长和细胞迁移。在多种癌症中，netrin - 1显示出促癌活力，这被认为是由于netrin-1与其受体结合促进了细胞的生存。
本研究发现，不同于全长分泌形式netrin-1，某些癌细胞通过一个非主流启动子启动表达产生一个截短的，核仁内形式的netrin-1（Delta-N netrin-1）。因为核仁定位信号位于其羧基端，Delta... |
Netrin-1 是一种分泌蛋白，能促进中枢神经系统的轴束生长和细胞迁移。在多种癌症中，netrin - 1显示出促癌活力，这被认为是由于netrin-1与其受体结合促进了细胞的生存。
本研究发现，不同于全长分泌形式netrin-1，某些癌细胞通过一个非主流启动子启动表达产生一个截短的，核仁内形式的netrin-1（Delta-N netrin-1）。因为核仁定位信号位于其羧基端，Delta-N netrin-1被定位于核仁内。它与核仁蛋白相互作用，影响核仁的超微结构，并与核糖体基因的启动子相互作用。
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此外，在体外实验中，Delta-N netrin-1刺激细胞增殖。Delta-N netrin-1同时促进体内的肿瘤生长。因此，癌细胞不仅通过产生一个全长分泌形式的netrin-1，促进细胞的存活，也通过产生截短形式的netrin-1提高核糖体合成，以刺激细胞增殖。
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080821501878.gif" 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/10.1126/scisignal.2002456" target="_blank">10.1016/j.cell.2011.10.017</a>
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<br/><strong>Nucleolar Localization of a Netrin-1 Isoform Enhances Tumor Cell Proliferation</strong><br/>
Céline Delloye-Bourgeois1*, David Goldschneider1*, Andrea Paradisi1*, Gabriel Therizols2*, Stéphane Belin2, Sabine Hacot2, Manuel Rosa-Calatrava3, Jean-Yves Scoazec4, Jean-Jacques Diaz2, Agnès Bernet1, and Patrick Mehlen1
Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (N-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, N-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, N-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.
<br/>来源：生物谷
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本研究发现，不同于全长分泌形式netrin-1，某些癌细胞通过一个非主流启动子启动表达产生一个截短的，核仁内形式的netrin-1（Delta-N netrin-1）。因为核仁定位信号位于其羧基端，Delta-N netrin-1被定位于核仁内。它与核仁蛋白相互作用，影响核仁的超微结构，并与核糖体基因的启动子相互作用。
<!--more-->
此外，在体外实验中，Delta-N netrin-1刺激细胞增殖。Delta-N netrin-1同时促进体内的肿瘤生长。因此，癌细胞不仅通过产生一个全长分泌形式的netrin-1，促进细胞的存活，也通过产生截短形式的netrin-1提高核糖体合成，以刺激细胞增殖。
<div id="ztload">
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080821501878.gif" 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/10.1126/scisignal.2002456" target="_blank">10.1016/j.cell.2011.10.017</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Nucleolar Localization of a Netrin-1 Isoform Enhances Tumor Cell Proliferation</strong><br/>
Céline Delloye-Bourgeois1*, David Goldschneider1*, Andrea Paradisi1*, Gabriel Therizols2*, Stéphane Belin2, Sabine Hacot2, Manuel Rosa-Calatrava3, Jean-Yves Scoazec4, Jean-Jacques Diaz2, Agnès Bernet1, and Patrick Mehlen1
Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (N-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, N-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, N-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.
<br/>来源：生物谷
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