人工肽通过钙神经蛋白-TFEB途径抑制自噬。

IF 4.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-09-30 DOI:10.1016/j.bbamcr.2024.119853

Yumeng Yang , Yanan Li , Hanxiao Shang , Yueyang Liu , Wenying Li , Limin Chen , Na Cheng , Yuchen Zhang , Nan Zhang , Yanxia Yin , Li Tong , Zhimei Li , Jingyu Yang , Jing Luo

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引用次数: 0

摘要

我们以前曾报道过一种生物活性肽（pep3）能有效抑制纯化的钙调磷酸酶（CN）的酶活性。在本文中，我们进一步证明了转染的 pep3 能强烈抑制 HEK293 细胞中 CN 的酶活性。转录因子 EB（TFEB）作为 CN 的底物之一，在自噬-溶酶体通路（ALP）中发挥着重要作用，因此我们研究了 pep3 对 CN-TFEB-ALP 通路的影响。Pep3能明显抑制TFEB下游基因的mRNA水平、自噬相关蛋白的表达以及HEK293细胞的自噬通量。我们还在小鼠体内验证了 pep3 对自噬的抑制作用。这些发现为发现更多的CN抑制剂和自噬抑制药物提供了新思路。

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An artificial peptide inhibits autophagy through calcineurin-TFEB pathway

We previously reported that a bioactive peptide (pep3) can potently inhibit the enzyme activity of purified calcineurin (CN). In this paper, we further demonstrate that transfected pep3 can strongly inhibit CN enzyme activity in HEK293 cells. Transcription factor EB (TFEB) plays an important role in the autophagy-lysosome pathway (ALP) as one of the substrates of CN, so we study the effect of pep3 on the CN-TFEB-ALP pathway. Pep3 can significantly inhibit the mRNA levels of the TFEB downstream genes and the expression of the autophagy-associated proteins, and autophagy flux in HEK293 cells. We also validated the inhibitory effect of pep3 on autophagy in mice. These findings may provide a new idea for discovering more CN inhibitors and autophagy inhibitory drugs.

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来源期刊

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.