Proteomics Analysis Reveals Novel RASSF2 Interaction Partners
Proteomics Analysis Reveals Novel RASSF2 Interaction Partners
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DOI：
10.3390/cancers8030037
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发表时间：
2016-03-01
期刊：
影响因子：
5.2
通讯作者：
Donninger, Howard
中科院分区：
文献类型：
--
作者：
Barnoud, Thibaut;Wilkey, Daniel W.;Donninger, Howard
RASSF2是一种肿瘤抑制因子，与其他RAS相关结构域(RASSF)家族成员具有相同的同源性。它是一种强大的促凋亡K-RAS效应器，在许多人类肿瘤中经常失活。RASSF2的确切作用机制尚不清楚，但它可能作为支架蛋白，调节其他促凋亡效应分子的活性，从而调节和整合肿瘤抑制通路。然而，到目前为止，只确定了数量有限的RASSF2互动伙伴。我们使用了一种基于蛋白质组学的方法来确定额外的RASSF2相互作用，从而更好地了解RASSF2的作用机制。我们鉴定了几种蛋白质，包括C1QBP、Vimentin、蛋白磷酸酶1G和核糖核酸酶抑制因子，它们在多种生物学过程中发挥作用，包括蛋白质翻译后修饰、上皮-间充质转化、细胞迁移和氧化还原动态平衡，这些都是以前没有报道的与RASSF2相互作用的蛋白。我们独立验证了其中两个新的相互作用，C1QBP和Vimentin，发现与C1QBP的相互作用被K-RAS增强，而有趣的是，Vimentin相互作用被K-RAS减弱。此外，RASSF2/K-RAS调节Vimentin的乙酰化。因此，我们的数据揭示了RASSF2可能发挥其功能的新机制，其中一些可能是受RAS调节的。
RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated.