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乙酰转移酶 p300 对肿瘤调控的影响:从翻译后蛋白质修饰的新视角。

Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification.

机构信息

National Center for International Research of Bio-Targeting Theranostics, Guangxi Key Laboratory of Bio-Targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-Targeting Theranostics, Guangxi Medical University, Nanning 530021, China.

National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Biomolecules. 2023 Feb 22;13(3):417. doi: 10.3390/biom13030417.

Abstract

p300 acts as a transcription coactivator and an acetyltransferase that plays an important role in tumourigenesis and progression. In previous studies, it has been confirmed that p300 is an important regulator in regulating the evolution of malignant tumours and it also has extensive functions. From the perspective of non-posttranslational modification, it has been proven that p300 can participate in regulating many pathophysiological processes, such as activating oncogene transcription, promoting tumour cell growth, inducing apoptosis, regulating immune function and affecting embryo development. In recent years, p300 has been found to act as an acetyltransferase that catalyses a variety of protein modification types, such as acetylation, propanylation, butyylation, 2-hydroxyisobutyration, and lactylation. Under the catalysis of this acetyltransferase, it plays its crucial tumourigenic driving role in many malignant tumours. Therefore, the function of p300 acetyltransferase has gradually become a research hotspot. From a posttranslational modification perspective, p300 is involved in the activation of multiple transcription factors and additional processes that promote malignant biological behaviours, such as tumour cell proliferation, migration, and invasion, as well as tumour cell apoptosis, drug resistance, and metabolism. Inhibitors of p300 have been developed and are expected to become novel anticancer drugs for several malignancies. We review the characteristics of the p300 protein and its functional role in tumour from the posttranslational modification perspective, as well as the current status of p300-related inhibitor research, with a view to gaining a comprehensive understanding of p300.

摘要

p300 作为转录共激活因子和乙酰转移酶,在肿瘤发生和进展中发挥着重要作用。在之前的研究中,已经证实 p300 是调节恶性肿瘤进化的重要调节剂,它也具有广泛的功能。从非翻译后修饰的角度来看,已经证明 p300 可以参与调节许多生理病理过程,如激活癌基因转录、促进肿瘤细胞生长、诱导细胞凋亡、调节免疫功能和影响胚胎发育。近年来,p300 被发现作为一种乙酰转移酶,可催化多种蛋白质修饰类型,如乙酰化、丙酰化、丁酰化、2-羟基异丁酰化和乳酰化。在这种乙酰转移酶的催化下,它在许多恶性肿瘤中发挥着关键的致癌驱动作用。因此,p300 乙酰转移酶的功能逐渐成为研究热点。从翻译后修饰的角度来看,p300 参与激活多种转录因子和促进恶性生物学行为的附加过程,如肿瘤细胞增殖、迁移和侵袭,以及肿瘤细胞凋亡、耐药性和代谢。已经开发出了 p300 的抑制剂,并有望成为几种恶性肿瘤的新型抗癌药物。我们从翻译后修饰的角度综述了 p300 蛋白的特性及其在肿瘤中的功能作用,以及 p300 相关抑制剂研究的现状,以期全面了解 p300。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3782/10046601/f6cb0cead1be/biomolecules-13-00417-g001.jpg

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