Department of Cell Biology and Physiology, University of New Mexico School of Medicine and University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.
Wiley Interdiscip Rev RNA. 2018 Mar;9(2). doi: 10.1002/wrna.1462. Epub 2018 Jan 11.
RNA binding proteins (RBPs) play key roles in RNA dynamics, including subcellular localization, translational efficiency and metabolism. Cold-inducible RNA binding protein (CIRP) is a stress-induced protein that was initially described as a DNA damage-induced transcript (A18 hnRNP), as well as a cold-shock domain containing cold-stress response protein (CIRBP) that alters the translational efficiency of its target messenger RNAs (mRNAs). This review summarizes recent work on the roles of CIRP in the context of inflammation and cancer. The function of CIRP in cancer appeared to be solely driven though its functions as an RBP that targeted cancer-associated mRNAs, but it is increasingly clear that CIRP also modulates inflammation. Several recent studies highlight roles for CIRP in immune responses, ranging from sepsis to wound healing and tumor-promoting inflammation. While modulating inflammation is an established role for RBPs that target cytokine mRNAs, CIRP appears to modulate inflammation by several different mechanisms. CIRP has been found in serum, where it binds the TLR4-MD2 complex, acting as a Damage-associated molecular pattern (DAMP). CIRP activates the NF-κB pathway, increasing phosphorylation of Iκκ and IκBα, and stabilizes mRNAs encoding pro-inflammatory cytokines. While CIRP promotes higher levels of pro-inflammatory cytokines in certain cancers, it also decreases inflammation to accelerate wound healing. This dichotomy suggests that the influence of CIRP on inflammation is context dependent and highlights the importance of detailing the mechanisms by which CIRP modulates inflammation. WIREs RNA 2018, 9:e1462. doi: 10.1002/wrna.1462 This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
RNA 结合蛋白（RBPs）在 RNA 动力学中发挥着关键作用，包括亚细胞定位、翻译效率和代谢。冷诱导 RNA 结合蛋白（CIRP）是一种应激诱导蛋白，最初被描述为一种 DNA 损伤诱导转录物（A18 hnRNP），以及一种含有冷应激反应蛋白（CIRBP）的冷休克域，该蛋白改变其靶信使 RNA（mRNA）的翻译效率。这篇综述总结了最近关于 CIRP 在炎症和癌症背景下的作用的研究工作。CIRP 在癌症中的功能似乎完全是通过其作为靶向癌症相关 mRNA 的 RBP 的功能来驱动的，但越来越清楚的是，CIRP 也调节炎症。最近的几项研究强调了 CIRP 在免疫反应中的作用，从败血症到伤口愈合和促进肿瘤炎症。虽然调节炎症是靶向细胞因子 mRNA 的 RBPs 的既定作用，但 CIRP 似乎通过几种不同的机制来调节炎症。CIRP 已在血清中被发现，在血清中它与 TLR4-MD2 复合物结合，充当损伤相关分子模式（DAMP）。CIRP 激活 NF-κB 途径，增加 Iκκ 和 IκBα 的磷酸化，并稳定编码促炎细胞因子的 mRNA。虽然 CIRP 在某些癌症中促进更高水平的促炎细胞因子，但它也会降低炎症以加速伤口愈合。这种二分法表明，CIRP 对炎症的影响取决于上下文，并强调了详细阐述 CIRP 调节炎症的机制的重要性。WIREs RNA 2018, 9:e1462. doi: 10.1002/wrna.1462 本文归类于：RNA 在疾病与发育中 > RNA 在疾病中 RNA 与蛋白质和其他分子的相互作用 > 蛋白-RNA 相互作用：功能意义
