A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins.
A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins.
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DOI：
10.1002/bies.202200014
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发表时间：
2022-06
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--
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细胞中的分子伴侣不断监测并结合新合成蛋白质中暴露的疏水性，并协助它们折叠或靶向细胞膜以插入。然而，蛋白质可能错误折叠或错误定位，这通常导致疏水性氨基酸暴露于含水胞质溶胶。同样，分子伴侣识别这些蛋白质中暴露的疏水性，以防止对细胞有害的非特异性相互作用和聚集。分子伴侣结合的错误折叠的蛋白质，然后用泛素链表示它们的蛋白酶体降解装饰。分子伴侣是如何仅仅基于其暴露的疏水信号来介导新生蛋白质的成熟和错误折叠蛋白质的泛素化的，这仍然是个谜。在这篇综述中，我们提出了一个动态的泛素化和去泛素化模型，其中新合成的蛋白质的泛素化作为一个“修复我”的信号，无论是可溶性蛋白质的重折叠或重定向膜蛋白的帮助下的伴侣和去泛素化。这种模型将为异常新生蛋白质折叠或膜插入路线提供额外的时间，从而避免过度的蛋白质降解并节省用于蛋白质合成的细胞能量。新生蛋白质有错误折叠、泛素化和蛋白酶体降解的风险。然而，泛素化并不总是意味着蛋白质的终结。我们提出了一个模型，使用泛素化作为错误折叠的新生蛋白质的“修复我”信号。泛素化可以募集解折叠酶、去泛素化酶和分子伴侣，为异常的新生蛋白质正确折叠提供额外的机会。
Molecular chaperones in cells constantly monitor and bind to exposed hydrophobicity in newly synthesized proteins and assist them in folding or targeting to cellular membranes for insertion. However, proteins can be misfolded or mistargeted, which often causes hydrophobic amino acids to be exposed to the aqueous cytosol. Again, chaperones recognize exposed hydrophobicity in these proteins to prevent nonspecific interactions and aggregation, which are harmful to cells. The chaperone-bound misfolded proteins are then decorated with ubiquitin chains denoting them for proteasomal degradation. It remains enigmatic how molecular chaperones can mediate both maturation of nascent proteins and ubiquitination of misfolded proteins solely based on their exposed hydrophobic signals. In this review, we propose a dynamic ubiquitination and deubiquitination model in which ubiquitination of newly synthesized proteins serves as a “fix me” signal for either refolding of soluble proteins or retargeting of membrane proteins with the help of chaperones and deubiquitinases. Such a model would provide additional time for aberrant nascent proteins to fold or route for membrane insertion, thus avoiding excessive protein degradation and saving cellular energy spent on protein synthesis. Nascent proteins are at risk of misfolding, ubiquitination, and proteasomal degradation. However, ubiquitination does not always signify the end for proteins. We propose a model that uses ubiquitination as a “fix me” signal for misfolded nascent proteins. Ubiquitination may recruit unfolding enzymes, deubiquitinases, and chaperones to provide additional chances for aberrant nascent proteins to fold properly.
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影响因子：
8.8
作者：
Chio, Un Seng;Chung, SangYoon;Shan, Shu-ou
通讯作者：
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DOI：
10.1111/febs.15638
发表时间：
2021-09
期刊：
The FEBS journal
影响因子：
--
作者：
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通讯作者：
Walters KJ
影响因子：
64.8
作者：
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通讯作者：
Hegde, Ramanujan S.