Biochemical Characterisation of Human Transglutaminase 4
Transglutaminases are protein-modifying enzymes involved in physiological and pathological processes with potent therapeutic possibilities. Human TG4, also called prostate transglutaminase, is involved in the development of autoimmune and tumour diseases. Although rodent TG4 is well characterised, b...
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2021
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oai:doaj.org-article:9371c1dddc8d46e9915d6dadfe600e1b2021-11-25T17:56:44ZBiochemical Characterisation of Human Transglutaminase 410.3390/ijms2222124481422-00671661-6596https://doaj.org/article/9371c1dddc8d46e9915d6dadfe600e1b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12448https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Transglutaminases are protein-modifying enzymes involved in physiological and pathological processes with potent therapeutic possibilities. Human TG4, also called prostate transglutaminase, is involved in the development of autoimmune and tumour diseases. Although rodent TG4 is well characterised, biochemical characteristics of human TG4 that could help th e understanding of its way of action are not published. First, we analysed proteomics databases and found that TG4 protein is present in human tissues beyond the prostate. Then, we studied in vitro the transamidase activity of human TG4 and its regulation using the microtitre plate method. Human TG4 has low transamidase activity which prefers slightly acidic pH and a reducing environment. It is enhanced by submicellar concentrations of SDS suggesting that membrane proximity is an important regulatory event. Human TG4 does not bind GTP as tested by GTP-agarose and BODIPY-FL-GTPγS binding, and its proteolytic activation by dispase or when expressed in AD-293 cells was not observed either. We identified several potential human TG4 glutamine donor substrates in the AD-293 cell extract by biotin-pentylamine incorporation and mass spectrometry. Several of these potential substrates are involved in cell–cell interaction, adhesion and proliferation, suggesting that human TG4 could become an anticancer therapeutic target.Zsuzsa Csobán-SzabóBálint BécsiSaïd El AlaouiLászló FésüsIlma Rita Korponay-SzabóRóbert KirályMDPI AGarticletransglutaminaseTG4TGpprotein crosslinkingenzyme activitysubstrate searchBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12448, p 12448 (2021) |
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transglutaminase TG4 TGp protein crosslinking enzyme activity substrate search Biology (General) QH301-705.5 Chemistry QD1-999 |
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transglutaminase TG4 TGp protein crosslinking enzyme activity substrate search Biology (General) QH301-705.5 Chemistry QD1-999 Zsuzsa Csobán-Szabó Bálint Bécsi Saïd El Alaoui László Fésüs Ilma Rita Korponay-Szabó Róbert Király Biochemical Characterisation of Human Transglutaminase 4 |
| description |
Transglutaminases are protein-modifying enzymes involved in physiological and pathological processes with potent therapeutic possibilities. Human TG4, also called prostate transglutaminase, is involved in the development of autoimmune and tumour diseases. Although rodent TG4 is well characterised, biochemical characteristics of human TG4 that could help th e understanding of its way of action are not published. First, we analysed proteomics databases and found that TG4 protein is present in human tissues beyond the prostate. Then, we studied in vitro the transamidase activity of human TG4 and its regulation using the microtitre plate method. Human TG4 has low transamidase activity which prefers slightly acidic pH and a reducing environment. It is enhanced by submicellar concentrations of SDS suggesting that membrane proximity is an important regulatory event. Human TG4 does not bind GTP as tested by GTP-agarose and BODIPY-FL-GTPγS binding, and its proteolytic activation by dispase or when expressed in AD-293 cells was not observed either. We identified several potential human TG4 glutamine donor substrates in the AD-293 cell extract by biotin-pentylamine incorporation and mass spectrometry. Several of these potential substrates are involved in cell–cell interaction, adhesion and proliferation, suggesting that human TG4 could become an anticancer therapeutic target. |
| format |
article |
| author |
Zsuzsa Csobán-Szabó Bálint Bécsi Saïd El Alaoui László Fésüs Ilma Rita Korponay-Szabó Róbert Király |
| author_facet |
Zsuzsa Csobán-Szabó Bálint Bécsi Saïd El Alaoui László Fésüs Ilma Rita Korponay-Szabó Róbert Király |
| author_sort |
Zsuzsa Csobán-Szabó |
| title |
Biochemical Characterisation of Human Transglutaminase 4 |
| title_short |
Biochemical Characterisation of Human Transglutaminase 4 |
| title_full |
Biochemical Characterisation of Human Transglutaminase 4 |
| title_fullStr |
Biochemical Characterisation of Human Transglutaminase 4 |
| title_full_unstemmed |
Biochemical Characterisation of Human Transglutaminase 4 |
| title_sort |
biochemical characterisation of human transglutaminase 4 |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/9371c1dddc8d46e9915d6dadfe600e1b |
| work_keys_str_mv |
AT zsuzsacsobanszabo biochemicalcharacterisationofhumantransglutaminase4 AT balintbecsi biochemicalcharacterisationofhumantransglutaminase4 AT saidelalaoui biochemicalcharacterisationofhumantransglutaminase4 AT laszlofesus biochemicalcharacterisationofhumantransglutaminase4 AT ilmaritakorponayszabo biochemicalcharacterisationofhumantransglutaminase4 AT robertkiraly biochemicalcharacterisationofhumantransglutaminase4 |
| _version_ |
1718411817080848384 |