Inhibition of nuclear import and cell-cycle progression by mutated forms of the dynamin-like GTPase MxB
Inhibition of nuclear import and cell-cycle progression by mutated forms of the dynamin-like GTPase MxB
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DOI：
10.1073/pnas.0403167101
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发表时间：
2004-06-15
影响因子：
11.1
通讯作者：
Lemmon, MA
中科院分区：
文献类型：
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作者：
King, MC;Raposo, G;Lemmon, MA
Mx蛋白形成动力蛋白样GTP酶的亚家族，其在细胞运输中具有良好的作用。一些Mx蛋白（例如，人MxA）具有抗病毒活性，并受I型IFN严格调节。其他（例如，人MxB）缺乏抗病毒活性，并被认为具有尚不清楚的正常细胞功能。与这一假设相一致，我们报告说，MxB的表达没有IFN治疗。MxB似乎是专门的核内，并集中在细胞质面的核孔，这表明在其调节的作用。我们发现显性阴性（GTP酶缺陷）MxB突变体的表达有效地阻断了核输入，并导致G（1）/S细胞周期进程的延迟。使用RNA干扰（RNAi）的MxB耗竭导致类似的细胞周期缺陷，但不阻止核输入。因此，MxB本身似乎不是核输入所必需的，而是可以调节其效率和/或动力学。这些研究表明，一个动力蛋白样蛋白在核质运输中的作用出乎意料，并表明相关功能可能被其抗病毒亲属篡夺。
Mx proteins form a subfamily of the dynamin-like GTPases, which have well established roles in cellular trafficking. Some Mx proteins (e.g., human MxA) have antiviral activity and are tightly regulated by type I IFNs. Others (e.g., human MxB) lack antiviral activity and are thought to have normal cellular functions that remain undefined. Consistent with this hypothesis, we report that MxB is expressed without IFN treatment. MxB seems to be exclusively extranuclear and is concentrated at the cytoplasmic face of nuclear pores, suggesting a role in their regulation. We find that expression of dominant negative (GTPase-defective) MxB mutants efficiently blocks nuclear import and causes a delay in G(1)/S cell-cycle progression. MxB depletion using RNA interference (RNAi) leads to a similar cell-cycle defect but does not block nuclear import. MxB therefore seems not to be required for nuclear import per se but may instead regulate its efficiency and/or kinetics. These studies indicate an unexpected role for a dynamin-like protein in nucleocytoplasmic trafficking and suggest that a related function might be usurped by its antiviral relatives.