Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48UFD1/NPL4, a ubiquitin-selective chaperone
Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48UFD1/NPL4, a ubiquitin-selective chaperone
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DOI：
10.1016/s0092-8674(01)00595-5
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发表时间：
2001-11-30
期刊：
影响因子：
64.5
通讯作者：
Jentsch, S
中科院分区：
文献类型：
--
作者：
Rape, M;Hoppe, T;Jentsch, S
酵母的OLE途径调节er结合酶δ 9-脂肪酸去饱和酶OLE1的水平，从而控制膜的流动性。该调控的一个核心组成部分是转录因子SPT23，它是哺乳动物NF-kappaB的同源物。SPT23是一种无活性的内质网膜锚定前体，通过调控的泛素/蛋白酶体依赖性加工（RUP）激活。我们现在发现SPT23在加工前二聚化，加工后的分子p90保留其泛素修饰，并最初与未加工的膜结合SPT23伴侣保持联系。随后，p90通过伴侣样CDC48（UFD1/NPL4）复合物的活性从其伴侣体中解放出来，用于核靶向。值得注意的是，该酶优先结合泛素化底物，这表明CDC48（UFD1/NPL4）有资格选择性地从蛋白质复合物中去除泛素偶联物。
The OLE pathway of yeast regulates the level of the ER-bound enzyme Delta9-fatty acid desaturase OLE1, thereby, controlling membrane fluidity. A central component of this regulon is the transcription factor SPT23, a homolog of mammalian NF-kappaB. SPT23 is synthesized as an inactive, ER membrane-anchored precursor that is activated by regulated ubiquitin/proteasome-dependent processing (RUP). We now show that SPT23 dimerizes prior to processing and that the processed molecule, p90, retains its ubiquitin modification and initially remains tethered to its unprocessed, membrane-bound SPT23 partner. Subsequently, p90 is liberated from its partner for nuclear targeting by the: activity of the chaperone-like CDC48(UFD1/NPL4) complex. Remarkably, this enzyme binds preferentially ubiquitinated substrates, suggesting that CDC48(UFD1/NPL4) is qualified to selectively remove ubiquitin conjugates from protein complexes.