Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila.
Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila.
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Tribbles假激酶对细胞生长和增殖的控制：来自果蝇的教训。
DOI：
10.3390/cancers13040883
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发表时间：
2021-02-20
期刊：
影响因子：
5.2
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Dobens LL;Nauman C;Fischer Z;Yao X
TRIBBLES假蛋白激酶是CAMK(钙/钙调蛋白依赖蛋白激酶)亚家族的一个分支，与多种癌症相关的疾病信号通路有关，包括黑色素瘤、肺癌、肝脏和急性白血病。这类分子调节细胞增殖的能力最早是在模式生物果蝇和果蝇遗传模型中被认识到的，并继续为这一家族调节正常发育和与其适当调节和功能破坏相关的疾病的分子机制提供洞察。Tribble(Trib)蛋白家族在细胞的正常发育和对环境胁迫的反应中调节细胞的生长、增殖和分化。人类Trib亚型(Trib1、2和3)的突变与代谢性疾病有关，并与白血病和实体肿瘤的形成有关，包括黑色素瘤、肝癌和肺癌。果蝇摩擦蛋白(Drodexila Tribble，TRBL)是第一个被发现的假蛋白激酶亚家族成员，具有保守的结构和相似的功能，可以结合和指导细胞生长和增殖的关键介质的降解。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，这导致了Trib家族成员横跨多个调节其生长促进活性的途径。最近使用果蝇模型的工作为保守的Tribble功能在干细胞静止、组织再生、与胰岛素信号有关的代谢以及与河马信号通路有关的肿瘤形成等新方面提供了重要的见解。在这里，我们重点介绍一些最近的研究，并讨论它们对理解TRIB在癌症和疾病病理学中所起的复杂作用的影响。
Tribbles pseudokinases represent a sub-branch of the CAMK (Ca2+/calmodulin-dependent protein kinase) subfamily and are associated with disease-associated signaling pathways associated with various cancers, including melanoma, lung, liver, and acute leukemia. The ability of this class of molecules to regulate cell proliferation was first recognized in the model organism Drosophila and the fruit fly genetic model and continues to provide insight into the molecular mechanism by which this family of adapter molecules regulates both normal development and disease associated with corruption of their proper regulation and function. 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.
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DOI：
10.1042/bj20141441
发表时间：
2015-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Bailey FP;Byrne DP;Oruganty K;Eyers CE;Novotny CJ;Shokat KM;Kannan N;Eyers PA
通讯作者：
Eyers PA
影响因子：
--
作者：
Blanco E;Ruiz-Romero M;Beltran S;Bosch M;Punset A;Serras F;Corominas M
通讯作者：
Corominas M
影响因子：
7.7
作者：
Gawlinski, Pawel;Nikolay, Rainer;Grosshans, Joerg
通讯作者：
Grosshans, Joerg
细胞介导的转化生长因子的共同作用：β型与正常大鼠肾细胞的孵育产生可溶性活性，从而延长对α类型的皱纹反应。
影响因子：
7.8
作者：
Myrdal, S E;Twardzik, D R;Auersperg, N
通讯作者：
Auersperg, N
影响因子：
13.3
作者：
Devis-Jauregui L;Eritja N;Davis ML;Matias-Guiu X;Llobet-Navàs D
通讯作者：
Llobet-Navàs D