Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN USA.
Cell Cycle. 2011 Apr 1;10(7):1043-9. doi: 10.4161/cc.10.7.15206.
Deoxyhypusine synthase (DHS) catalyzes the post-translational formation of the amino acid hypusine. Hypusine is unique to the eukaryotic translational initiation factor 5A (eIF5A), and is required for its functions in mRNA shuttling, translational elongation, and stress granule formation. In recent studies, we showed that DHS promotes cytokine and ER stress signaling in the islet β cell and thereby contributes to its dysfunction in the setting of diabetes mellitus. Here, we review the evidence supporting a role for DHS (and hypusinated eIF5A) in cellular stress responses, and provide new data on the phenotype of DHS knockout mice. We show that homozygous knockout mice are embryonic lethal, but heterozygous knockout mice appear normal with no evidence of growth or metabolic deficiencies. Mouse embryonic fibroblasts from heterozygous knockout mice attenuate acute cytokine signaling, as evidenced by reduced production of inducible nitric oxide synthase, but show no statistically significant defects in proliferation or cell cycle progression. Our data are discussed with respect to the utility of sub-maximal inhibition of DHS in the setting of inflammatory states, such as diabetes mellitus.
脱羟鸟氨酸合酶（DHS）催化氨基酸 hypusine 的翻译后形成。Hypusine 是真核翻译起始因子 5A（eIF5A）所特有的，是其在 mRNA 穿梭、翻译延伸和应激颗粒形成中的功能所必需的。在最近的研究中，我们表明 DHS 在胰岛 β 细胞中促进细胞因子和内质网应激信号转导，从而导致其在糖尿病状态下功能障碍。在这里，我们回顾了支持 DHS（和 hypusinated eIF5A）在细胞应激反应中的作用的证据，并提供了 DHS 敲除小鼠表型的新数据。我们表明，纯合敲除小鼠是胚胎致死的，但杂合敲除小鼠似乎正常，没有生长或代谢缺陷的证据。来自杂合敲除小鼠的小鼠胚胎成纤维细胞减弱了急性细胞因子信号，表现为诱导型一氧化氮合酶的产生减少，但在增殖或细胞周期进程方面没有统计学意义上的缺陷。我们的数据与 DHS 的亚最大抑制在炎症状态（如糖尿病）中的应用的效用有关。
