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Review
. 2021 May 10;10(5):1153.
doi: 10.3390/cells10051153.

The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review

Wenrui Zhang  1 , Yingying Lin  1
Affiliations
Review

The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review

Wenrui Zhang et al. Cells. .

Abstract

Asparagine endopeptidase (AEP), also called legumain, is currently the only known cysteine protease that specifically cleaves peptide bonds in asparaginyl residue in the mammalian genome. Since 2003, AEP has been reported to be widely expressed in a variety of carcinomas and is considered a potential therapeutic target. In the following years, researchers intensively investigated the substrates of AEP and the mechanism of AEP in partial tumors. With the identification of substrate proteins such as P53, integrin αvβ3, MMP-2, and MMP-9, the biochemical mechanism of AEP in carcinomas is also more precise. This review will clarify the probable mechanisms of AEP in the progression of breast carcinoma, glioblastoma, gastric carcinoma, and epithelial ovarian carcinoma. This review will also discuss the feasibility of targeted therapy with AEP inhibitor (AEPI) in these carcinomas.

Keywords: asparagine endopeptidase; breast cancer; epithelial ovarian cancer; gastric cancer; glioblastoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Crystal structure of human pro-AEP and AEP. (A) Crystal structure of human pro-AEP. The caspase-like catalytic domain is shown in yellow, the Activation Peptide in blue and the LSAM domain in pink; the C-terminal processing sites K289 and N323 are shown in red. (B) Crystal structure of human AEP. The active site residues (Asn42, His148, and Cys189) of the catalytic domain are shown in green. The figure was created using PYMOL.
Figure 2
Figure 2
Schematic diagram of AEP’s roles in several carcinomas. (A) The biochemical and regulation mechanism of AEP in GBM. (B) The biochemical and regulation mechanism of AEP in BC. (C) Schematic diagram of the biochemical mechanism and involved signaling pathway of AEP in EOC. (D) Schematic diagram of the involved signaling pathway and regulation mechanism of AEP in GC. The figure was created using BioRender.com.
Figure 3
Figure 3
Timeline of basic research in the field of AEP.
See this image and copyright information in PMC

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