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Review
. 2023 Nov 10;15(22):5363.
doi: 10.3390/cancers15225363.

Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression

Zijun Zhang  1 , Fenghuang Zhan  1
Affiliations
Review

Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression

Zijun Zhang et al. Cancers (Basel). .

Abstract

Cystatins are a family of intracellular and extracellular protease inhibitors that inhibit cysteine cathepsins-a group of lysosomal cysteine proteases that participate in multiple biological processes, including protein degradation and post-translational cleavage. Cysteine cathepsins are associated with the development of autoimmune diseases, tumor progression, and metastasis. Cystatins are categorized into three subfamilies: type 1, type 2, and type 3. The type 2 cystatin subfamily is the largest, containing 10 members, and consists entirely of small secreted proteins. Although type 2 cystatins have many shared biological roles, each member differs in structure, post-translational modifications (e.g., glycosylation), and expression in different cell types. These distinctions allow the type 2 cystatins to have unique biological functions and properties. This review provides an overview of type 2 cystatins, including their biological similarities and differences, their regulatory effect on human immune responses, and their roles in tumor progression, immune evasion, and metastasis.

Keywords: cathepsin; cystatin; immunity; inflammation; protease inhibitor; tumor progression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The categorization of cystatins. (B) The structure of cystatins. Using cystatin C as an example. The coordinate file was retrieved from RCSB PDB, id: 3GAX. The image was generated using PyMOL (Schrodinger). The green region represents the cathepsin inhibitory site and the yellow residue represents the LGMN inhibitory site. This structure was originally discovered and published by Kolodziejczyk et al. [6].
Figure 2
Figure 2
The schematic diagram of key region alignment of type 2 cystatin family. The sequence of each cystatin was retrieved from the NCBI GenPept database. Multiple sequence alignment was performed by Clustal Omega and Boxshade. The conserved G-QXVXG-VPW fragment is highlighted in red and post-helix N is highlighted in blue.
Figure 3
Figure 3
The overview of type 2 cystatins’ role on immune regulation and cancer development.
See this image and copyright information in PMC

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