Degradation of HNE-modified proteins - possible role of ubiquitin
Degradation of HNE-modified proteins - possible role of ubiquitin
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DOI：
10.1179/135100007x162130
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发表时间：
2007-02-01
期刊：
影响因子：
3.8
通讯作者：
Grune, Tilman
中科院分区：
文献类型：
--
作者：
Botzen, Diana;Grune, Tilman
4-羟基壬烯醛（HNE）是一种脂质过氧化产物，能够修饰蛋白质。hne修饰的蛋白质在相当程度上被蛋白酶体系统降解。目前尚不清楚对hne修饰蛋白的识别是否由泛素介导，或者是否涉及泛素不依赖的蛋白酶体途径。在这项研究中，我们证明了hne修饰的GAPDH在体外优先泛素化。为了证明在活细胞中多泛素化hne修饰蛋白的形成，我们探索了E36成纤维细胞。HNE蛋白修饰的明显增加可以在HNE处理后的细胞中得到证实。使用抑制剂，我们可以显示泛素依赖性、泛素非依赖性和溶酶体途径影响hne修饰蛋白的存在。我们得出的结论是，尽管存在几种降解hne修饰蛋白的蛋白水解途径，但泛素依赖性降解可能参与其中。
4-Hydroxynonenal (HNE) is a lipid peroxidation product that is able to modify proteins. HNE-modified proteins are degraded to a considerable extend by the proteasomal system. It is unclear whether the recognition of HNE-modified proteins is mediated by ubiquitin, or whether the ubiquitin-independent proteasomal pathway is involved. In this study we demonstrate that HNE-modified GAPDH is preferentially ubiquitinated in vitro. In an attempt to demonstrate the formation of poly-ubiquitinated HNE-modified proteins in living cells we explored E36 fibroblasts. A clear rise in HNE-protein modification could be demonstrated after HNE treatment of the cells. Using inhibitors, we could show that the ubiquitin-dependent, ubiquitin-independent, and the lysosomal pathways affect the presence of HNE-modified proteins. We conclude that, although several proteolytic pathways exist for the degradation of HNE-modified proteins, there is the possibility of involvement of ubiquitin-dependent degradation.