Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann Str. 26, 50931 Cologne, Germany.
Laboratory of Protein Metabolism in Development and Aging, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Bioessays. 2018 May;40(5):e1700223. doi: 10.1002/bies.201700223. Epub 2018 Apr 3.
The insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway is a pivotal genetic program regulating cell growth, tissue development, metabolic physiology, and longevity of multicellular organisms. IIS integrates a fine-tuned cascade of signaling events induced by insulin/IGF-1, which is precisely controlled by post-translational modifications. The ubiquitin/proteasome-system (UPS) influences the functionality of IIS through inducible ubiquitylation pathways that regulate internalization of the insulin/IGF-1 receptor, the stability of downstream insulin/IGF-1 signaling targets, and activity of nuclear receptors for control of gene expression. An age-related decline in UPS activity is often associated with an impairment of IIS, contributing to pathologies such as cancer, diabetes, cardiovascular, and neurodegenerative disorders. Recent findings identified a key role of diverse ubiquitin modifications in insulin signaling decisions, which governs dynamic adaption upon environmental and physiological changes. In this review, we discuss the mutual crosstalk between ubiquitin and insulin signaling pathways in the context of cellular and organismal homeostasis.
胰岛素/胰岛素样生长因子-1（IGF-1）信号通路（IIS）是一个关键的遗传程序，调节细胞生长、组织发育、代谢生理学和多细胞生物的寿命。IIS 整合了由胰岛素/IGF-1 诱导的精细信号事件级联，该级联受到翻译后修饰的精确控制。泛素/蛋白酶体系统（UPS）通过诱导泛素化途径影响 IIS 的功能，该途径调节胰岛素/IGF-1 受体的内化、下游胰岛素/IGF-1 信号靶标的稳定性以及核受体的活性，以控制基因表达。UPS 活性的年龄相关性下降通常与 IIS 的损害有关，导致癌症、糖尿病、心血管和神经退行性疾病等病理。最近的研究结果确定了各种泛素修饰在胰岛素信号决定中的关键作用，这些决定控制着环境和生理变化时的动态适应。在这篇综述中，我们讨论了泛素和胰岛素信号通路在细胞和机体稳态中的相互作用。
