A mammalian monothiol glutaredoxin, Grx3, is critical for cell cycle progression during embryogenesis.
A mammalian monothiol glutaredoxin, Grx3, is critical for cell cycle progression during embryogenesis.
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DOI：
10.1111/j.1742-4658.2011.08178.x
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Hirschi KD
中科院分区：
文献类型：
--
作者：
Cheng NH;Zhang W;Chen WQ;Jin J;Cui X;Butte NF;Chan L;Hirschi KD
谷氧还蛋白(Glutaredoxins，Grx)在维持活细胞氧化还原动态平衡方面起着至关重要的作用。最近，一个新出现的Grxs亚群被发现，它的活性基序中含有一个半胱氨酸残基(单硫醇Grxs)。然而，这类蛋白质的生物学和生理功能还没有得到很好的表征。在这里，我们描述了一种哺乳动物单硫醇GRX(Grx3，也称为TXNL2/Picot)，它与酵母ScGrx3/ScGrx4具有很高的相似性。在酵母表达实验中，哺乳动物Grx3s定位于细胞核，能够修复grx3grx4细胞的生长缺陷。此外，Grx3还抑制了酵母grx3gxr4细胞中铁的积累，并抑制了突变细胞对外源氧化剂的敏感性。在小鼠中，Grx3mRNA在发育中的胚胎、成体组织和器官中普遍表达，并在氧化应激中诱导表达。缺乏Grx3的小鼠胚胎变小，出现形态缺陷，最终在怀孕12.5天时死亡。对小鼠胚胎成纤维细胞的分析表明，Grx3DNA缺失使G2/M期细胞生长和细胞周期进程受阻，而S期的−/−复制不受Grx3DNA缺失的影响。此外，Grx3基因敲除的HeLa细胞在有丝分裂退出方面表现出明显的延迟，并具有更高的双核细胞比例。因此，我们的研究结果表明，哺乳动物Grx3具有保护细胞免受氧化应激的保守功能，并且Grx3基因的缺失会导致小鼠早期胚胎死亡，这可能是由于晚期有丝分裂过程中细胞周期进程的缺陷所致。
Glutaredoxins (Grxs) have been shown to be critical in maintaining redox homeostasis in living cells. Recently, an emerging subgroup of Grxs with one cysteine residue in the putative active motif (monothiol Grxs) has been identified. However, the biological and physiological functions of this group of proteins have not been well characterized. Here, we characterize a mammalian monothiol Grx (Grx3, also termed TXNL2 / PICOT) with high similarity to yeast ScGrx3 / ScGrx4. In yeast expression assays, mammalian Grx3s were localized to the nuclei and able to rescue growth defects of grx3grx4 cells. Furthermore, Grx3 inhibited iron accumulation in yeast grx3gxr4 cells and suppressed the sensitivity of mutant cells to exogenous oxidants. In mice, Grx3 mRNA was ubiquitously expressed in developing embryos, adult tissues and organs, and was induced during oxidative stress. Mouse embryos absent of Grx3 grew smaller with morphological defects and eventually died at 12.5 days of gestation. Analysis in mouse embryonic fibroblasts revealed that Grx3−/− cells had impaired growth and cell cycle progression at the G2/M phase, whereas the DNA replication during the S phase was not affected by Grx3 deletion. Furthermore, Grx3-knockdown HeLa cells displayed a significant delay in mitotic exit and had a higher percentage of binucleated cells. Therefore, our findings suggest that the mammalian Grx3 has conserved functions in protecting cells against oxidative stress and deletion of Grx3 in mice causes early embryonic lethality which could be due to defective cell cycle progression during late mitosis.
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影响因子：
4
作者：
Betts DH;Madan P
通讯作者：
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影响因子：
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作者：
Cha, Hyeseon;Kim, Ji Myoung;Oh, Jae Gyun;Jeong, Moon Hee;Park, Chang Sik;Park, Jaeho;Jeong, Hyeon Joo;Park, Byung Keon;Lee, Young-Hoon;Jeong, Dongtak;Yang, Dong Kwon;Bernecker, Oliver Y.;Kim, Do Han;Hajjar, Roger J.;Park, Woo Jin
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作者：
BUSHWELLER, JH;ASLUND, F;HOLMGREN, A
通讯作者：
HOLMGREN, A
影响因子：
11.4
作者：
Bandyopadhyay, Sibali;Gama, Filipe;Rouhier, Nicolas
通讯作者：
Rouhier, Nicolas