Obstruction of polyubiquitination affects PTS1 peroxisomal matrix protein import
Obstruction of polyubiquitination affects PTS1 peroxisomal matrix protein import
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DOI：
10.1016/j.bbamcr.2005.01.004
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发表时间：
2005-09-10
影响因子：
5.1
通讯作者：
van der Klei, IJ
中科院分区：
文献类型：
--
作者：
Kiel, JAKW;Otzen, M;van der Klei, IJ
Pex4p是一种泛素偶联酶，在过氧化物酶体基质蛋白输入的后期起作用。本研究表明，在甲基营养酵母中，多态汉斯菌（Hansenula polymorpha）产生的一种突变形式的泛素（Ub(K48R)）对PTS1基质蛋白的进口有显著影响。在缺乏Pex4p的细胞中没有观察到这种效应，在这种细胞中，过氧化物酶体的生物发生缺陷在很大程度上受到抑制。这些发现首次表明，Pex4p在基质蛋白进口中的功能涉及多泛素化。我们还证明了H. polymorpha中Ub（K48R）的产生会导致Pex5p的降解增强。在PEX4基因被删除的细胞中也进行了类似的观察。我们证明，在这两个菌株中，Pex5p的降解是由于泛素化和随后的蛋白酶体降解。这一过程似乎依赖于Pex5p n端（Lys21）的一个保守赖氨酸残基，在Pex5p（K21R）突变体中被阻止。我们推测，蛋白酶体对Pex5p的降解对于去除滞留在Pex5p介导的蛋白质进口途径后期的受体分子是重要的。(c) 2005 Elsevier B.V.版权所有
Pex4p is an ubiquitin-conjugating enzyme that functions at a late stage of peroxisomal matrix protein import. Here we show that in the methylotrophic yeast Hansenula polymorpha production of a mutant form of ubiquitin (Ub(K48R)) has a dramatic effect on PTS1 matrix protein import. This effect was not observed in cells lacking Pex4p, in which the peroxisome biogenesis defect was largely suppressed. These findings provide the first indication that the function of Pex4p in matrix protein import involves polyubiquitination. We also demonstrate that the production of Ub(K48R) in H. polymorpha results in enhanced Pex5p degradation. A similar observation was made in cells in which the PEX4 gene was deleted. We demonstrate that in both strains Pex5p degradation was due to ubiquitination and subsequent degradation by the proteasome. This process appeared to be dependent on a conserved lysine residue in the N-terminus of Pex5p (Lys21) and was prevented in a Pex5p(K21R) mutant. We speculate that the degradation of Pex5p by the proteasome is important to remove receptor molecules that are stuck at a late stage of the Pex5p-mediated protein import pathway. (c) 2005 Elsevier B.V. All rights reserved.