Differential modification of Ras proteins by ubiquitination
Differential modification of Ras proteins by ubiquitination
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DOI：
10.1016/j.molcel.2006.02.011
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发表时间：
2006-03-03
期刊：
影响因子：
16
通讯作者：
Bar-Sagi, D
中科院分区：
文献类型：
--
作者：
Jura, N;Scotto-Lavino, E;Bar-Sagi, D
Ras蛋白是控制细胞增殖、分化和存活的信号转导途径的重要组成部分。众所周知，Ras蛋白的功能多样性是通过其差异区室化来实现的，但控制其空间分离的机制尚未完全了解。在这里，我们表明，HRas是受泛素结合，而KRas是难治性的这种修改。HRas的膜锚定结构域对于指导HRas的单泛素化和双泛素化是必要且足够的。泛素与HRas的连接稳定了其与内体的结合，并调节其激活Raf/ MAPK信号通路的能力。因此，Ras蛋白的差异泛素化可能控制其位置特异性信号传导活性。
Ras proteins are essential components of signal transduction pathways that control cell proliferation, differentiation, and survival. It is well recognized that the functional versatility of Ras proteins is accomplished through their differential compartmentalization, but the mechanisms that control their spatial segregation are not fully understood. Here we show that HRas is subject to ubiquitin conjugation, whereas KRas is refractory to this modification. The membrane-anchoring domain of HRas is necessary and sufficient to direct the mono- and diubiquitination of HRas. Ubiquitin attachment to HRas stabilizes its association with endosomes and modulates its ability to activate the Raf/ MAPK signaling pathway. Therefore, differential ubiquitination of Ras proteins may control their location-specific signaling activities.