Role of FIP200 in inflammatory processes beyond its canonical autophagy function.
Role of FIP200 in inflammatory processes beyond its canonical autophagy function.
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DOI：
10.1042/bst20191156
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发表时间：
2020-07
影响因子：
3.9
通讯作者：
S. Yeo;Chenran Wang;J. Guan
中科院分区：
文献类型：
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作者：
S. Yeo;Chenran Wang;J. Guan
FIP200 （RB1CC1）是典型巨噬的关键调节因子，也是选择性自噬和炎症过程的关键调节因子。在分子水平上阐明FIP200在自噬中的作用的同时，也有研究表明其自噬功能在哺乳动物的生理过程和病理环境（如癌症）中的重要性。然而，越来越多的人认识到，大多数（如果不是全部的话）自噬基因也在其他过程中发挥作用，如lc3相关的吞噬、囊泡运输和蛋白质分泌。因此，这导致了产生自噬基因的特异性突变体的努力，这些突变体更容易被解剖其自噬与非自噬功能。在这方面，我们已经产生了一个FIP200敲入小鼠等位基因，该等位基因在典型巨噬中存在缺陷。这揭示了FIP200的典型自噬独立功能，该功能负责限制促炎信号。在这篇综述中，我们将讨论FIP200在这一过程中的作用，对癌症免疫治疗的影响，并强调具体剖析FIP200不同功能的关键前景途径。
FIP200 (RB1CC1) is a critical regulator of canonical macroautophagy and has also emerged as a crucial regulator of selective autophagy as well as inflammatory processes. The illumination of FIP200's role in autophagy at the molecular level has been accompanied by studies demonstrating the importance of its autophagy function in physiological processes in mammals and pathological contexts such as cancer. However, there is an increasing appreciation that most, if not all of the autophagy genes, also play a role in other processes such as LC3-associated phagocytosis, vesicle trafficking and protein secretion. Consequently, this has led to efforts in generating specific mutants of autophagy genes that are more amenable to dissecting their autophagy versus non-autophagy functions. In this aspect, we have generated a FIP200 knock-in mouse allele that is defective for canonical macroautophagy. This has revealed a canonical-autophagy-independent function of FIP200 that is responsible for limiting pro-inflammatory signaling. In this review, we will discuss FIP200's role in this process, the implications with regards to cancer immunotherapy and highlight key prospective avenues to specifically dissect the distinct functions of FIP200.