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The non-linearity of RAF-MEK signaling in dendritic cells.
Cell Cycle ( IF 3.4 ) Pub Date : 2020-08-04 , DOI: 10.1080/15384101.2020.1795990
Kristina Riegel 1 , Krishnaraj Rajalingam 1
Affiliation  

Kinases form the major part of the druggable genome and their selective inhibition in human cancers has had reasonable clinical success. In contrast to tumorigenesis, the role of kinases in mediating immune responses is poorly understood. However, synergistic therapeutic regimens combining targeted therapy and immune therapy have been found to increase the median survival of tumor patients. In this context, we uncovered that RAF and MEK1/2 kinases, which are the integral parts of the classical MAPK cascade, have unique roles in driving DC differentiation and activation. RAF kinases are stabilized in their protein levels during DC differentiation and are obligatory for normal functioning of DCs. But, the targeting of MEK1/2 kinases with specific inhibitors did not phenocopy the effects observed with RAF inhibitors suggesting that RAF and MEK1/2 kinases may have specific and unique roles in driving immune responses, which deserves further studies to successfully administer these inhibitors in clinics.



中文翻译:

树突细胞中 RAF-MEK 信号的非线性。

激酶构成了可成药基因组的主要部分,它们在人类癌症中的选择性抑制已经取得了合理的临床成功。与肿瘤发生相反,激酶在介导免疫反应中的作用知之甚少。然而,已经发现结合靶向治疗和免疫治疗的协同治疗方案可以增加肿瘤患者的中位生存期。在这种情况下,我们发现 RAF 和 MEK1/2 激酶是经典 MAPK 级联的组成部分,在驱动 DC 分化和激活方面具有独特的作用。在 DC 分化过程中,RAF 激酶的蛋白质水平稳定,并且是 DC 正常功能所必需的。但,

更新日期:2020-09-23
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