分泌蛋白的自噬:癌症的治疗靶点。

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Kewal Kumar Mahapatra, Srimanta Patra, Soumya Ranjan Mishra, Bishnu Prasad Behera, Shankargouda Patil, Sujit Kumar Bhutia
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引用次数: 1

摘要

自噬是一种经典的细胞降解分解代谢过程,在真核细胞中也具有功能离散的非降解作用。它对常规和非常规的蛋白质分泌(降解性和分泌性自噬,分别具有不同的溶酶体降解和细胞外排出)途径具有关键的调节作用。含有蛋白质的n -氨基末端先导蛋白序列遵循常规的分泌途径,而无先导蛋白则选择分泌自噬。分泌性自噬过程包括核心自噬机制蛋白,特别是ULK1/2、Beclin 1、LC3和GABARAP,并与高尔基重组和堆叠蛋白(GRASPs)协调。分泌性大泌体与质膜融合,将细胞质货物排出到细胞外环境。另外,分泌性大泌体也与多泡体(MVBs)融合并协调escrt(复合体I;TSG101)和Rab GTPase释放到细胞外空间。自噬与多种蛋白质的分泌有关,这些蛋白质参与细胞信号传导、炎症和癌变。分泌蛋白通过维持细胞增殖,抑制细胞凋亡,促进血管生成和转移,调节免疫细胞,调节细胞能量代谢,以及对抗癌药物的耐药性,在癌症中发挥重要作用。肿瘤发生过程中自噬调节的复杂性依赖于蛋白质分泌途径。自噬调节的tor -自噬空间偶联室复合体激活促炎细胞因子和无领导蛋白如HMGB1的分泌。最后,本章综述了自噬在调节常规和非常规蛋白质分泌途径中的作用及其在癌症中的可能作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autophagy for secretory protein: Therapeutic targets in cancer.

Autophagy, a classical cellular degradative catabolic process, also involves a functionally discrete non-degradative role in eukaryotic cells. It imparts critical regulatory function on conventional and unconventional protein secretion (degradative and secretory autophagy with distinct lysosomal degradation and extracellular expulsion, respectively) pathways. The N-amino terminal leader sequence containing proteins follows a conventional secretion pathway, while the leader-less proteins opt for secretory autophagy. The secretory autophagic process ensembles core autophagy machinery proteins, specifically ULK1/2, Beclin 1, LC3, and GABARAP, in coordination with Golgi re-assembly and stacking proteins (GRASPs). The secretory omegasomes fuse with the plasma membrane for the expulsion of cytosolic cargos to the extracellular environment. Alternatively, the secretory omegasomes also fuse with multi-vesicular bodies (MVBs) and harmonize ESCRTs (Complex I; TSG101) and Rab GTPase for their release to extracellular space. Autophagy has been associated with the secretion of diverse proteins involved in cellular signaling, inflammation, and carcinogenesis. Secreted proteins play an essential role in cancer by sustaining cell proliferation, inhibiting apoptosis, enhancing angiogenesis and metastasis, immune cell regulation, modulation of cellular energy metabolism, and resistance to anticancer drugs. The complexity of autophagy regulation during tumorigenesis is dependent on protein secretion pathways. Autophagy-regulated TOR-autophagy spatial coupling compartment complex energizes enhanced secretion of pro-inflammatory cytokines and leaderless proteins such as HMGB1. In conclusion, the chapter reviews the role of autophagy in regulating conventional and unconventional protein secretion pathways and its possible role in cancer.

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来源期刊
Advances in protein chemistry and structural biology
Advances in protein chemistry and structural biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
7.40
自引率
0.00%
发文量
66
审稿时长
>12 weeks
期刊介绍: Published continuously since 1944, The Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics.
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