Ruiz-Cantos Miriam, Hutchison Claire E, Shoulders Carol C
Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ 1, UK.
Cancers (Basel). 2021 Sep 8;13(18):4517. doi: 10.3390/cancers13184517.
This commentary integrates historical and modern findings that underpin our understanding of the cell-specific functions of the Tribbles (TRIB) proteins that bear on tumorigenesis. We touch on the initial discovery of roles played by mammalian TRIB proteins in a diverse range of cell-types and pathologies, for example, TRIB1 in regulatory T-cells, TRIB2 in acute myeloid leukaemia and TRIB3 in gliomas; the origins and diversity of transcripts; microRNA-mediated (miRNA) regulation of transcript decay and translation; the substantial conformational changes that ensue on binding of TRIB1 to the transcription factor C/EBPα; and the unique pocket formed by TRIB1 to sequester its C-terminal motif bearing a binding site for the E3 ubiquitin ligase COP1. Unashamedly, the narrative is relayed through the perspective of the Tribbles Research and Innovation Network, and its establishment, progress and future ambitions: the growth of TRIB and COP1 research to hasten discovery of their cell-specific contributions to health and obesity-related cancers.
本评论整合了历史和现代研究结果，这些结果支撑了我们对与肿瘤发生相关的Tribbles（TRIB）蛋白细胞特异性功能的理解。我们阐述了哺乳动物TRIB蛋白在多种细胞类型和病理过程中所起作用的最初发现，例如，调节性T细胞中的TRIB1、急性髓系白血病中的TRIB2和神经胶质瘤中的TRIB3；转录本的起源和多样性；微小RNA（miRNA）介导的转录本降解和翻译调控；TRIB1与转录因子C/EBPα结合后发生的显著构象变化；以及TRIB1形成的独特口袋，用于隔离其带有E3泛素连接酶COP1结合位点的C末端基序。毫不掩饰地说，本文是通过Tribbles研究与创新网络的视角来叙述的，以及它的建立、进展和未来抱负：TRIB和COP1研究的发展，以加速发现它们对健康和肥胖相关癌症的细胞特异性贡献。
