引言

Prenylation（戊烯酰化）是一种脂质修饰过程，涉及将戊烯基或异戊二烯基异戊二烯醇共价地连接到蛋白质的保守半胱氨酸残基上。这个过程对许多蛋白质的正常功能至关重要，包括核层蛋白、真菌交配因子、Ras和Ras相关的GTP结合蛋白、蛋白激酶以及至少一种病毒蛋白。Prenylation（戊烯酰化）促进了大多数这些蛋白质与细胞膜的相互作用，这并不令人意外，因为涉及的脂质具有疏水性。此外，戊烯酰化似乎在涉及这些物种的几种蛋白质相互作用中起着重要作用。本综述主要关注戊烯蛋白质加工的酶学过程和戊烯酰化在细胞事件中的功能意义。

分子机制和功能影响

戊烯酰化是一个复杂的过程，涉及几个酶促步骤。第一步是将异戊二烯基或戊烯基基团添加到目标蛋白质的半胱氨酸残基上。然后通过蛋白酶的剪切作用去除蛋白质的末端氨基酸，暴露出戊烯酰化的半胱氨酸残基。最后一步是向戊烯酰化的半胱氨酸残基添加一个甲基基团。

戊烯酰化在许多蛋白质的正常功能中起着至关重要的作用。例如，Ras蛋白质的戊烯酰化对其正确定位到细胞质膜和激活下游信号通路的能力至关重要。核层蛋白的戊烯酰化对核膜的正确组装和核结构的维持非常重要。蛋白激酶的戊烯酰化对其正确定位到细胞质膜和与其他信号蛋白的相互作用非常重要。

发展和进展

近年来，在我们对蛋白质戊烯酰化的分子机制和功能后果的理解方面取得了重大进展。几项研究已经确定了新的戊烯酰化蛋白质，并揭示了戊烯酰化在各种细胞过程中的作用。例如，已经发现戊烯酰化在自噬的调节中起到了一定作用，自噬是细胞降解和回收受损或不必要的细胞成分的过程。戊烯酰化也被证明在免疫反应调节和癌症发展中起到了作用。

应用

蛋白质戊烯酰化在细胞过程中的重要性促使开发了几种针对戊烯酰化的药物。例如，已经开发了戊烯酰转移酶抑制剂（FTIs）作为潜在的抗癌治疗药物。这些药物抑制戊烯酰转移酶的活性，该酶对Ras蛋白质的戊烯酰化至关重要。通过抑制Ras蛋白质的戊烯酰化，FTIs阻止了促进细胞生长和增殖的下游信号通路的激活。已经对几种FTIs进行了临床试验，并且有些药物在作为抗癌治疗药物方面显示出了希望。

结论

总之，蛋白质戊烯酰化是一个复杂的过程，对许多蛋白质的正常功能起着至关重要的作用。最近的研究揭示了戊烯酰化的分子机制和功能后果，并确定了新的戊烯酰化蛋白质和戊烯酰化在细胞过程中的新角色。戊烯酰化在细胞过程中的重要性促使开发了几种针对戊烯酰化的药物，包括FTIs，这些药物在作为抗癌治疗药物方面显示出了希望。

Citations:

[1] Zhang, F. L., & Casey, P. J. (1996). Protein prenylation: molecular mechanisms and functional consequences. Annual review of biochemistry, 65(1), 241-269.https://www.scienceopen.com/document?vid=2c7a9717-9294-4adb-94ff-9b7b9b1d1a92

[2] https://en.wikipedia.org/wiki/Prenylation

## Introduction

Protein prenylation is a lipid modification process that involves the covalent attachment of either farnesyl or geranylgeranyl isoprenoids to conserved cysteine residues of proteins. This process is essential for the proper functioning of many proteins, including nuclear lamins, fungal mating factors, Ras and Ras-related GTP-binding proteins, protein kinases, and at least one viral protein. Prenylation promotes membrane interactions of most of these proteins, which is not surprising given the hydrophobicity of the lipids involved. In addition, prenylation appears to play a major role in several protein-protein interactions involving these species. The emphasis in this review is on the enzymology of prenyl protein processing and the functional significance of prenylation in cellular events.

## Molecular Mechanisms and Functional Consequences

Prenylation is a complex process that involves several enzymatic steps. The first step is the addition of an isoprenoid group to the cysteine residue of the target protein. This is followed by proteolytic cleavage of the terminal amino acids of the protein, which exposes the prenylated cysteine residue. The final step involves the addition of a methyl group to the prenylated cysteine residue.

Prenylation plays a crucial role in the proper functioning of many proteins. For example, prenylation of Ras proteins is essential for their proper localization to the plasma membrane and their ability to activate downstream signaling pathways. Prenylation of nuclear lamins is important for the proper assembly of the nuclear envelope and the maintenance of nuclear structure. Prenylation of protein kinases is important for their proper localization to the plasma membrane and their ability to interact with other signaling proteins.

## Development and Progress

In recent years, there has been significant progress in our understanding of the molecular mechanisms and functional consequences of protein prenylation. Several studies have identified new prenylated proteins and have shed light on the role of prenylation in various cellular processes. For example, prenylation has been shown to play a role in the regulation of autophagy, a process by which cells degrade and recycle damaged or unnecessary cellular components. Prenylation has also been shown to play a role in the regulation of the immune response and in the development of cancer.

## Applications

The importance of protein prenylation in cellular processes has led to the development of several drugs that target prenylation. For example, farnesyltransferase inhibitors (FTIs) have been developed as potential cancer therapeutics. These drugs inhibit the activity of farnesyltransferase, which is required for the prenylation of Ras proteins. By inhibiting Ras prenylation, FTIs prevent the activation of downstream signaling pathways that promote cell growth and proliferation. Several FTIs have been tested in clinical trials, and some have shown promise as cancer therapeutics.

## Conclusion

In conclusion, protein prenylation is a complex process that plays a crucial role in the proper functioning of many proteins. Recent studies have shed light on the molecular mechanisms and functional consequences of prenylation, and have identified new prenylated proteins and new roles for prenylation in cellular processes. The importance of prenylation in cellular processes has led to the development of several drugs that target prenylation, including FTIs, which have shown promise as cancer therapeutics.

Citations:

[1] https://www.scienceopen.com/document?vid=2c7a9717-9294-4adb-94ff-9b7b9b1d1a92

[2] https://pubmed.ncbi.nlm.nih.gov/8811180/

[3] https://www.sciencedirect.com/science/article/abs/pii/S1388198100000093

[4] https://www.annualreviews.org/doi/abs/10.1146/annurev.bi.65.070196.001325

[5] https://en.wikipedia.org/wiki/Prenylation

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