Selective degradation of oxidatively modified protein substrates by the proteasome
Selective degradation of oxidatively modified protein substrates by the proteasome
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DOI：
10.1016/s0006-291x(03)00809-x
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发表时间：
2003-06-06
影响因子：
3.1
通讯作者：
Davies, KJA
中科院分区：
文献类型：
--
作者：
Grune, T;Merker, K;Davies, KJA
哺乳动物细胞中的氧化应激是其有氧代谢的必然结果。氧化剂对蛋白质产生修饰，导致功能丧失（或获得不期望的功能），并且经常导致氧化蛋白质的降解增强。几年来，人们已经知道蛋白酶体参与氧化蛋白的降解。这篇综述总结了我们对蛋白酶体在体外系统中识别氧化蛋白底物及其对活细胞的适用性的认识。该领域的大多数研究都认为，轻度氧化蛋白质的降解是蛋白酶体系统的重要功能。底物的主要识别基序似乎是由20S“核心”蛋白酶体识别的疏水表面补丁。这样的疏水表面补丁是通过氧化过程中疏水氨基酸残基的部分解折叠和暴露而形成的。氧化蛋白质似乎是相对较差的泛素化底物，并且泛素化系统似乎不参与氧化蛋白质的识别或靶向。严重氧化的蛋白质似乎首先聚集（新的疏水键和离子键），然后形成共价交联，使它们对蛋白质水解具有高度抗性。不能降解广泛氧化的蛋白质可能有助于在疾病和衰老过程中蛋白质聚集体的积累。(C)2003 Elsevier Science（美国）。All rights reserved.
Oxidative stress in mammalian cells is an inevitable consequence of their aerobic metabolism. Oxidants produce modifications to proteins leading to loss of function (or gain of undesirable function) and very often to an enhanced degradation of the oxidized proteins. For several years it has been known that the proteasome is involved in the degradation of oxidized proteins. This review summarizes our knowledge about the recognition of oxidized protein substrates by the proteasome in in vitro systems and its applicability to living cells. The majority of studies in the field agree that the degradation of mildly oxidized proteins is an important function of the proteasomal system. The major recognition motif of the substrates seems to be hydrophobic surface patches that are recognized by the 20S 'core' proteasome. Such hydrophobic surface patches are formed by partial unfolding and exposure of hydrophobic amino acid residues during oxidation. Oxidized proteins appear to be relatively poor substrates for ubiquitination, and the ubiquitination system does not seem to be involved in the recognition or targeting of oxidized proteins. Heavily oxidized proteins appear to first aggregate (new hydrophobic and ionic bonds) and then to form covalent cross-links that make them highly resistant to proteolysis. The inability to degrade extensively oxidized proteins may contribute to the accumulation of protein aggregates during diseases and the aging process. (C) 2003 Elsevier Science (USA). All rights reserved.