2. Academic Validation
  3. An artificial peptide inhibits autophagy through calcineurin-TFEB pathway

An artificial peptide inhibits autophagy through calcineurin-TFEB pathway

  • Biochim Biophys Acta Mol Cell Res. 2024 Dec;1871(8):119853. doi: 10.1016/j.bbamcr.2024.119853.
Yumeng Yang 1,  Yanan Li 1,  Hanxiao Shang 2,  Yueyang Liu 3,  Wenying Li 1,  Limin Chen 1,  Na Cheng 1,  Yuchen Zhang 1,  Nan Zhang 1,  Yanxia Yin 1,  Li Tong 1,  Zhimei Li 4,  Jingyu Yang 5,  Jing Luo 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology of Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 111016, China.
  • 3 Shenyang Key Laboratory of Vascular Biology, Science and Research Center, Department of Pharmacology, Shenyang Medical College, Shenyang, China.
  • 4 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. Electronic address: lizm1211@163.com.
  • 5 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 111016, China. Electronic address: yangjingyu@syphu.edu.cn.
  • 6 Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology of Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing 100875, China. Electronic address: luojing@bnu.edu.cn.
PMID: 39353470 DOI: 10.1016/j.bbamcr.2024.119853
Abstract

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.

Keywords

Autophagy-lysosome pathway; Calcineurin; Inhibitor; Pep3; Transcription factor EB.

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