Ras and rheb signaling in survival and cell death.
Ras and rheb signaling in survival and cell death.
复制标题
RAS和RHEB信号传导在生存和细胞死亡中。
DOI：
10.3390/cancers5020639
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发表时间：
2013-05-28
期刊：
影响因子：
5.2
通讯作者：
Heumann R
中科院分区：
文献类型：
--
作者：
Ehrkamp A;Herrmann C;Stoll R;Heumann R
癌症最明显的特征之一是细胞不受控制的增殖，部分原因是生长因子供应的独立性。有丝分裂信号的一个主要成分是RAS，一种小的GTP酶。它是第一个被发现的人类原癌基因，三十多年来一直被认为可以促进细胞的增殖和生长。RAS被证明在发育过程中支持生长因子非依赖性存活，并保护有丝分裂后神经元免受化学或机械损伤诱导的神经元退化。相反，对于特定的病理生理情况和细胞系统，已经表明RAS也可能促进细胞死亡。RAS相关家族的蛋白(RASF，特别是RASSF1和RASF5)是被RAS-GTP激活的肿瘤抑制因子，通过激活哺乳动物不育20-样蛋白(MST1)来触发细胞凋亡。与RAS不同的是，它们在许多类型的肿瘤中的表达被抑制，这使得Rassf蛋白成为了解RAS活性的不同影响的令人兴奋的模型。RAS信号转导的结果可能取决于其下游各种效应器的激活之间的平衡，从而决定细胞走向增殖或凋亡的命运。脑中富含RAS同源蛋白(Rheb)是RAS超家族的一种蛋白，通过哺乳动物靶标雷帕霉素(MTOR)途径促进细胞增殖、生长和再生。然而，最近的证据表明，根据细胞的情况，Rheb-mTOR途径可能会将其功能从促生长途径转换为细胞死亡途径。与RAS信号相反，对于Rheb来说，细胞环境可能分别调节整个Rheb-mTOR途径走向细胞死亡或生存。
One of the most obvious hallmarks of cancer is uncontrolled proliferation of cells partly due to independence of growth factor supply. A major component of mitogenic signaling is Ras, a small GTPase. It was the first identified human protooncogene and is known since more than three decades to promote cellular proliferation and growth. Ras was shown to support growth factor-independent survival during development and to protect from chemical or mechanical lesion-induced neuronal degeneration in postmitotic neurons. In contrast, for specific patho-physiological cases and cellular systems it has been shown that Ras may also promote cell death. Proteins from the Ras association family (Rassf, especially Rassf1 and Rassf5) are tumor suppressors that are activated by Ras-GTP, triggering apoptosis via e.g., activation of mammalian sterile 20-like (MST1) kinase. In contrast to Ras, their expression is suppressed in many types of tumours, which makes Rassf proteins an exciting model for understanding the divergent effects of Ras activity. It seems likely that the outcome of Ras signaling depends on the balance between the activation of its various downstream effectors, thus determining cellular fate towards either proliferation or apoptosis. Ras homologue enriched in brain (Rheb) is a protein from the Ras superfamily that is also known to promote proliferation, growth, and regeneration through the mammalian target of rapamycin (mTor) pathway. However, recent evidences indicate that the Rheb-mTor pathway may switch its function from a pro-growth into a cell death pathway, depending on the cellular situation. In contrast to Ras signaling, for Rheb, the cellular context is likely to modulate the whole Rheb-mTor pathway towards cellular death or survival, respectively.