Functions of glutaminyl cyclase and its isoform in diseases
Glutaminyl cyclase (QC; isoform: isoQC) is a zinc-dependent enzyme that catalyzes the intramolecular cyclization of N-terminal glutamine and glutamic acid residues into a pyroglutamate residue (pGlu). This conversion is a type of posttranslational modification called pyroglutamylation. The expressio...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
EDP Sciences
2023-01-01
|
| Series: | Visualized Cancer Medicine |
| Subjects: | |
| Online Access: | https://vcm.edpsciences.org/articles/vcm/full_html/2023/01/vcm20220009/vcm20220009.html |
| _version_ | 1797333850338099200 |
|---|---|
| author | Liu Yu’e Shi Yufeng Wang Ping |
| author_facet | Liu Yu’e Shi Yufeng Wang Ping |
| author_sort | Liu Yu’e |
| collection | DOAJ |
| description | Glutaminyl cyclase (QC; isoform: isoQC) is a zinc-dependent enzyme that catalyzes the intramolecular cyclization of N-terminal glutamine and glutamic acid residues into a pyroglutamate residue (pGlu). This conversion is a type of posttranslational modification called pyroglutamylation. The expression of QC/isoQC is regulated by epigenetics, cell homeostasis, and its substrates. Pyroglutamylation is an important maturation process during the synthesis and secretion of hormones, functioning in different diseases, such as Alzheimer’s disease, tumors, and other kinds of chronic diseases mediated by inflammation. IsoQC has been identified as a key regulator of the CD47-SIRPα checkpoint and is critical for the pyroglutamylation of CD47 at its SIRPα binding site, thus helping cancer cells evade immune surveillance. Inhibition of isoQC blocks the interaction between CD47 and SIRPα, leading to constrained tumor growth, indicating that isoQC is a novel target for immunotherapy. Targeting isoQC overcomes the side effects of targeting CD47 because isoQC is Golgi resident and is not expressed on erythrocytes. Small molecules and antibodies have been developed to target isoQC, and some of them have been tested in preclinical or clinical studies. Here, we briefly review the discovery history of QC/isoQC and then discuss its regulation and function in different diseases, emphasizing the unique role of isoQC in immunotherapy. Finally, we summarize the development of inhibitors and their progress in clinical trials with the hope of providing useful insights for future investigation of QC/isoQC and targeting it in various diseases. |
| first_indexed | 2024-03-08T08:11:02Z |
| format | Article |
| id | doaj.art-f149e7d05397412894f355acf0ad437b |
| institution | Directory Open Access Journal |
| issn | 2740-4218 |
| language | English |
| last_indexed | 2024-03-08T08:11:02Z |
| publishDate | 2023-01-01 |
| publisher | EDP Sciences |
| record_format | Article |
| series | Visualized Cancer Medicine |
| spelling | doaj.art-f149e7d05397412894f355acf0ad437b2024-02-02T08:42:52ZengEDP SciencesVisualized Cancer Medicine2740-42182023-01-014110.1051/vcm/2022008vcm20220009Functions of glutaminyl cyclase and its isoform in diseasesLiu Yu’e0https://orcid.org/0000-0002-9240-869XShi Yufeng1https://orcid.org/0000-0003-3833-1035Wang Ping2Tongji University Cancer Center, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji UniversityTongji University Cancer Center, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji UniversityTongji University Cancer Center, Shanghai Tenth People’s Hospital of Tongji University, School of Medicine, Tongji UniversityGlutaminyl cyclase (QC; isoform: isoQC) is a zinc-dependent enzyme that catalyzes the intramolecular cyclization of N-terminal glutamine and glutamic acid residues into a pyroglutamate residue (pGlu). This conversion is a type of posttranslational modification called pyroglutamylation. The expression of QC/isoQC is regulated by epigenetics, cell homeostasis, and its substrates. Pyroglutamylation is an important maturation process during the synthesis and secretion of hormones, functioning in different diseases, such as Alzheimer’s disease, tumors, and other kinds of chronic diseases mediated by inflammation. IsoQC has been identified as a key regulator of the CD47-SIRPα checkpoint and is critical for the pyroglutamylation of CD47 at its SIRPα binding site, thus helping cancer cells evade immune surveillance. Inhibition of isoQC blocks the interaction between CD47 and SIRPα, leading to constrained tumor growth, indicating that isoQC is a novel target for immunotherapy. Targeting isoQC overcomes the side effects of targeting CD47 because isoQC is Golgi resident and is not expressed on erythrocytes. Small molecules and antibodies have been developed to target isoQC, and some of them have been tested in preclinical or clinical studies. Here, we briefly review the discovery history of QC/isoQC and then discuss its regulation and function in different diseases, emphasizing the unique role of isoQC in immunotherapy. Finally, we summarize the development of inhibitors and their progress in clinical trials with the hope of providing useful insights for future investigation of QC/isoQC and targeting it in various diseases.https://vcm.edpsciences.org/articles/vcm/full_html/2023/01/vcm20220009/vcm20220009.htmlglutaminyl cyclaseqpctlpyroglutamylationphagocytosiscd47isoqc |
| spellingShingle | Liu Yu’e Shi Yufeng Wang Ping Functions of glutaminyl cyclase and its isoform in diseases Visualized Cancer Medicine glutaminyl cyclase qpctl pyroglutamylation phagocytosis cd47 isoqc |
| title | Functions of glutaminyl cyclase and its isoform in diseases |
| title_full | Functions of glutaminyl cyclase and its isoform in diseases |
| title_fullStr | Functions of glutaminyl cyclase and its isoform in diseases |
| title_full_unstemmed | Functions of glutaminyl cyclase and its isoform in diseases |
| title_short | Functions of glutaminyl cyclase and its isoform in diseases |
| title_sort | functions of glutaminyl cyclase and its isoform in diseases |
| topic | glutaminyl cyclase qpctl pyroglutamylation phagocytosis cd47 isoqc |
| url | https://vcm.edpsciences.org/articles/vcm/full_html/2023/01/vcm20220009/vcm20220009.html |
| work_keys_str_mv | AT liuyue functionsofglutaminylcyclaseanditsisoformindiseases AT shiyufeng functionsofglutaminylcyclaseanditsisoformindiseases AT wangping functionsofglutaminylcyclaseanditsisoformindiseases |