Dobens Leonard L, Nauman Christopher, Fischer Zachary, Yao Xiaolan
Department of Genetics, Developmental and Evolutionary Biology, School of Biological and Chemical Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
Cancers (Basel). 2021 Feb 20;13(4):883. doi: 10.3390/cancers13040883.
The Tribbles (Trib) family of pseudokinase proteins regulate cell growth, proliferation, and differentiation during normal development and in response to environmental stress. Mutations in human Trib isoforms (Trib1, 2, and 3) have been associated with metabolic disease and linked to leukemia and the formation of solid tumors, including melanomas, hepatomas, and lung cancers. Drosophila Tribbles (Trbl) was the first identified member of this sub-family of pseudokinases and shares a conserved structure and similar functions to bind and direct the degradation of key mediators of cell growth and proliferation. Common Trib targets include Akt kinase (also known as protein kinase B), C/EBP (CAAT/enhancer binding protein) transcription factors, and Cdc25 phosphatases, leading to the notion that Trib family members stand athwart multiple pathways modulating their growth-promoting activities. Recent work using the Drosophila model has provided important insights into novel facets of conserved Tribbles functions in stem cell quiescence, tissue regeneration, metabolism connected to insulin signaling, and tumor formation linked to the Hippo signaling pathway. Here we highlight some of these recent studies and discuss their implications for understanding the complex roles Tribs play in cancers and disease pathologies.
Tribbles（Trib）伪激酶蛋白家族在正常发育过程中以及对环境应激作出反应时，调节细胞生长、增殖和分化。人类Trib亚型（Trib1、2和3）的突变与代谢疾病相关，并与白血病以及实体瘤（包括黑色素瘤、肝癌和肺癌）的形成有关。果蝇Tribbles（Trbl）是该伪激酶亚家族中第一个被鉴定的成员，它具有保守的结构，并且在结合和指导细胞生长与增殖的关键介质降解方面具有相似的功能。常见的Trib靶标包括Akt激酶（也称为蛋白激酶B）、C/EBP（CAAT/增强子结合蛋白）转录因子和Cdc25磷酸酶，这使得人们认为Trib家族成员阻碍了多种调节其生长促进活性的途径。最近利用果蝇模型开展的研究，为Tribbles在干细胞静止、组织再生、与胰岛素信号相关的代谢以及与Hippo信号通路相关的肿瘤形成等保守功能的新方面提供了重要见解。在此，我们重点介绍其中一些最新研究，并讨论它们对于理解Tribs在癌症和疾病病理中所起复杂作用的意义。
