Central Laboratory of Yan'nan Hospital Affiliated to Kunming, Medical University, Key Laboratory of Cardiovascular Diseases of Yunnan Province, Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, No. 245, Renmin East Road, Kunming, 650000, Yunnan, China.
Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Mol Cell Biochem. 2024 Jun;479(6):1415-1441. doi: 10.1007/s11010-023-04800-5. Epub 2023 Jul 13.
Mammalian autophagy-related protein Atg8, including the LC3 subfamily and GABARAP subfamily. Atg8 proteins play a vital role in autophagy initiation, autophagosome formation and transport, and autophagy-lysosome fusion. GABARAP subfamily proteins (GABARAPs) share a high degree of homology with LC3 family proteins, and their unique roles are often overlooked. GABARAPs are as indispensable as LC3 in autophagy. Deletion of GABARAPs fails autophagy flux induction and autophagy lysosomal fusion, which leads to the failure of autophagy. GABARAPs are also involved in the transport of selective autophagy receptors. They are engaged in various particular autophagy processes, including mitochondrial autophagy, endoplasmic reticulum autophagy, Golgi autophagy, centrosome autophagy, and dorphagy. Furthermore, GABARAPs are closely related to the transport and delivery of the inhibitory neurotransmitter γ-GABA and the angiotensin II AT1 receptor (AT1R), tumor growth, metastasis, and prognosis. GABARAPs also have been confirmed to be involved in various diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In order to better understand the role and therapeutic potential of GABARAPs, this article comprehensively reviews the autophagic and non-autophagic functions of GABARAPs, as well as the research progress of the role and mechanism of GABARAPs in cancer, cardiovascular diseases and neurodegenerative diseases. It emphasizes the significance of GABARAPs in the clinical prevention and treatment of diseases, and may provide new therapeutic ideas and targets for human diseases. GABARAP and GABARAPL1 in the serum of cancer patients are positively correlated with the prognosis of patients, which can be used as a clinical biomarker, predictor and potential therapeutic target.
哺乳动物自噬相关蛋白 Atg8，包括 LC3 亚家族和 GABARAP 亚家族。Atg8 蛋白在自噬起始、自噬体形成和运输以及自噬溶酶体融合中发挥着重要作用。GABARAP 亚家族蛋白（GABARAPs）与 LC3 家族蛋白具有高度同源性，但其独特的作用往往被忽视。GABARAPs 在自噬中与 LC3 一样不可或缺。GABARAPs 的缺失会导致自噬通量诱导和自噬溶酶体融合失败，从而导致自噬失败。GABARAPs 还参与选择性自噬受体的运输。它们参与各种特定的自噬过程，包括线粒体自噬、内质网自噬、高尔基体自噬、中心体自噬和多噬。此外，GABARAPs 与抑制性神经递质 γ-GABA 和血管紧张素 II AT1 受体（AT1R）的运输和递呈密切相关，与肿瘤的生长、转移和预后有关。GABARAPs 也被证实与各种疾病有关，如癌症、心血管疾病和神经退行性疾病。为了更好地理解 GABARAPs 的作用和治疗潜力，本文全面综述了 GABARAPs 的自噬和非自噬功能，以及 GABARAPs 在癌症、心血管疾病和神经退行性疾病中的作用和机制的研究进展。本文强调了 GABARAPs 在疾病临床预防和治疗中的意义，可能为人类疾病提供新的治疗思路和靶点。癌症患者血清中的 GABARAP 和 GABARAPL1 与患者的预后呈正相关，可作为临床生物标志物、预测因子和潜在治疗靶点。
