Regulating the regulator: post-translational modification of RAS.

Regulating the regulator: post-translational modification of RAS.
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DOI:
10.1038/nrm3255
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发表时间:
2011-12-22
期刊:
Nature reviews. Molecular cell biology
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Ras蛋白是单体GTP酶,作为二元分子开关来调节广泛的细胞过程。Ras上GDP与GTP的交换受鸟嘌呤核苷酸交换因子(GEFs)和GTP酶激活蛋白(GAPs)的调节,它们在不共价修饰Ras的情况下调节其激活状态。相比之下,Ras蛋白的翻译后修饰(PTMs)将它们导向各种细胞膜,并且在某些情况下,调节GTP - GDP交换。重要的Ras翻译后修饰包括通过法尼基化、蛋白水解和甲基化对其C末端CAAX基序进行的组成性和不可逆的重塑、可逆的棕榈酰化,以及包括磷酸化、肽基 - 脯氨酰异构化、单泛素化和双泛素化、亚硝基化、ADP核糖基化和糖基化在内的条件性修饰。
Ras proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on Ras is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which regulate the activation state of Ras without covalently modifying it. In contrast, post-translational modifications (PTMs) of Ras proteins direct them to various cellular membranes and, in some cases, modulate GTP–GDP exchange. Important Ras PTMs include the constitutive and irreversible remodelling of its C-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications including phosphorylation, peptidyl-proly isomerisation, mono- and di-ubiquitination, nitrosylation, ADP ribosylation and glucosylation.
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