McAvera Roisin M, Crawford Lisa J
Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.
Cancers (Basel). 2020 Jul 28;12(8):2094. doi: 10.3390/cancers12082094.
Genomic instability is a hallmark of cancer cells which results in excessive DNA damage. To counteract this, cells have evolved a tightly regulated DNA damage response (DDR) to rapidly sense DNA damage and promote its repair whilst halting cell cycle progression. The DDR functions predominantly within the context of chromatin and requires the action of chromatin-binding proteins to coordinate the appropriate response. TRIM24, TRIM28, TRIM33 and TRIM66 make up the transcriptional intermediary factor 1 (TIF1) family of chromatin-binding proteins, a subfamily of the large tripartite motif (TRIM) family of E3 ligases. All four TIF1 proteins are aberrantly expressed across numerous cancer types, and increasing evidence suggests that TIF1 family members can function to maintain genome stability by mediating chromatin-based responses to DNA damage. This review provides an overview of the TIF1 family in cancer, focusing on their roles in DNA repair, chromatin regulation and cell cycle regulation.
基因组不稳定是癌细胞的一个标志，它会导致过多的DNA损伤。为了应对这种情况，细胞进化出了一种严格调控的DNA损伤反应（DDR），以快速感知DNA损伤并促进其修复，同时停止细胞周期进程。DDR主要在染色质的背景下起作用，需要染色质结合蛋白的作用来协调适当的反应。TRIM24、TRIM28、TRIM33和TRIM66构成了染色质结合蛋白的转录中介因子1（TIF1）家族，它是E3连接酶的大三结构域（TRIM）家族的一个亚家族。所有四种TIF1蛋白在多种癌症类型中均异常表达，越来越多的证据表明，TIF1家族成员可通过介导基于染色质的DNA损伤反应来维持基因组稳定性。本综述概述了TIF1家族在癌症中的作用，重点关注它们在DNA修复、染色质调控和细胞周期调控中的作用。
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