Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Member of the German Center for Lung Research, Friedrichstrasse 24, D-35392 Giessen, Germany.
Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Member of the German Center for Lung Research, Friedrichstrasse 24, D-35392 Giessen, Germany.
Biochim Biophys Acta Mol Cell Res. 2019 Oct;1866(10):1676-1686. doi: 10.1016/j.bbamcr.2019.04.009. Epub 2019 Apr 25.
The three canonical members of the family of homeodomain-interacting protein (HIP) kinases fulfill overlapping and distinct roles in cellular stress response pathways. Here we systematically compared all three endogenous HIPKs for their intracellular distribution and mutual interactions. The endogenous HIPKs are contained in high molecular weight complexes of ~700 kDa but do not directly interact physically. Under basal conditions, HIPK1 was mostly cytoplasmic, while HIPK3 was found in the nucleus and HIPK2 occurred in both compartments. Inhibition of nuclear export by leptomycin B resulted in the nuclear accumulation of mainly HIPK1 and HIPK2, indicating constitutive dynamic nucleocytoplasmic shuttling. The carcinogenic chemical stressor sodium arsenite caused the induction of HIPK2-dependent cell death and also resulted in a rapid and complete nuclear translocation of HIPK2, showing that the intracellular distribution of this kinase can undergo dynamic regulation.
家庭同源结构域相互作用蛋白激酶（HIP）的三个规范成员在细胞应激反应途径中发挥重叠且不同的作用。在这里，我们系统地比较了所有三种内源性 HIPK，以研究它们的细胞内分布和相互作用。内源性 HIPK 包含在约 700 kDa 的高分子量复合物中，但它们之间没有直接的物理相互作用。在基础条件下，HIPK1 主要位于细胞质中，而 HIPK3 位于细胞核中，HIPK2 则存在于细胞质和细胞核中。莱普霉素 B 抑制核输出导致主要是 HIPK1 和 HIPK2 的核积累，表明其存在组成型的核质穿梭。致癌化学应激物砷酸钠诱导 HIPK2 依赖性细胞死亡，同时还导致 HIPK2 的快速和完全核转位，表明该激酶的细胞内分布可以进行动态调节。
