Insights from the protein interaction Universe of the multifunctional "Goldilocks" kinase DYRK1A.
Insights from the protein interaction Universe of the multifunctional "Goldilocks" kinase DYRK1A.
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DOI：
10.3389/fcell.2023.1277537
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
人双特异性酪氨酸（Y）调节激酶1A（DYRK 1A）由位于人21号染色体的唐氏综合征关键区域的剂量依赖性基因编码。DYRK 1A的已知底物包括参与转录、细胞周期控制、DNA修复和其他过程的蛋白质。然而，这种激酶的功能和调节并不完全清楚，目前的知识并不能完全解释这种激酶的剂量依赖性功能。最近的几项蛋白质组学研究在几种人类细胞系中鉴定了DYRK 1A相互作用蛋白。有趣的是，DYRK 1A的几种已知蛋白质底物在这些研究中检测不到，可能是由于激酶-底物相互作用的瞬时性质。可能的是，更强的结合DYRK 1A相互作用蛋白，其中许多是不好的特点，参与调节功能，通过招募DYRK 1A的特定亚细胞区室或不同的信号通路。更好地了解这些DYRK 1A相互作用的蛋白质可以帮助解码在胚胎发育和成年生物体中由这种重要的蛋白激酶调节的细胞过程。在这里，我们回顾了DYRK 1A蛋白质-蛋白质相互作用网络的生化和功能表征的现有知识，并讨论了其在人类疾病中的参与。
Human Dual specificity tyrosine (Y)-Regulated Kinase 1A (DYRK1A) is encoded by a dosage-dependent gene located in the Down syndrome critical region of human chromosome 21. The known substrates of DYRK1A include proteins involved in transcription, cell cycle control, DNA repair and other processes. However, the function and regulation of this kinase is not fully understood, and the current knowledge does not fully explain the dosage-dependent function of this kinase. Several recent proteomic studies identified DYRK1A interacting proteins in several human cell lines. Interestingly, several of known protein substrates of DYRK1A were undetectable in these studies, likely due to a transient nature of the kinase-substrate interaction. It is possible that the stronger-binding DYRK1A interacting proteins, many of which are poorly characterized, are involved in regulatory functions by recruiting DYRK1A to the specific subcellular compartments or distinct signaling pathways. Better understanding of these DYRK1A-interacting proteins could help to decode the cellular processes regulated by this important protein kinase during embryonic development and in the adult organism. Here, we review the current knowledge of the biochemical and functional characterization of the DYRK1A protein-protein interaction network and discuss its involvement in human disease.
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