Tissue Transglutaminase Is an In Situ Substrate of Calpain: Regulation of Activity
| Autor: | Rodney P. Guttmann, Gail V.W. Johnson, Jianwen Zhang |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
GTP' Tissue transglutaminase Proteolysis medicine.medical_treatment Antineoplastic Agents tau Proteins Cysteine Proteinase Inhibitors Biochemistry Substrate Specificity Neuroblastoma Cellular and Molecular Neuroscience chemistry.chemical_compound Cyclins Ribavirin Tumor Cells Cultured medicine Humans Enzyme Inhibitors Maitotoxin Enzyme Precursors Transglutaminases Protease medicine.diagnostic_test biology Calpain Oxocins Trypsin Molecular biology Diazomethane chemistry Guanosine 5'-O-(3-Thiotriphosphate) biology.protein Calcium Marine Toxins Oligopeptides Tiazofurin medicine.drug |
| Zdroj: | Journal of Neurochemistry. 71:240-247 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the transamidation of specific polypeptide-bound glutamine residues, a reaction that is inhibited by GTP. There is also preliminary evidence that, in situ, calpain and GTP may regulate tTG indirectly by modulating its turnover by the calcium-activated protease calpain. In the present study, the in vitro and in situ proteolysis of tTG by calpain, and modulation of this process by GTP, was examined. tTG is an excellent substrate for calpain and is rapidly degraded. Previously it has been demonstrated that GTP binding protects tTG from degradation by trypsin. In a similar manner, guanosine-5'-O-(3-thiotriphosphate) protects tTG against proteolysis by calpain. Treatment of SH-SY5Y cells with 1 nM maitotoxin, which increases intracellular calcium levels, resulted in a significant increase in in situ TG activity, with only a slight decrease in tTG protein levels. In contrast, when GTP levels were depleted by pretreating the cells with tiazofurin, maitotoxin treatment resulted in an approximately 50% decrease in tTG protein levels, and a significant decrease in TG activity, compared with maitotoxin treatment alone. Addition of calpain inhibitors inhibited the degradation of tTG in response to the combined treatment of maitotoxin and tiazofurin and resulted in a significant increase in in situ TG activity. These studies indicate that tTG is an endogenous substrate of calpain and that GTP selectively inhibits the degradation of tTG by calpain. |
| Databáze: | OpenAIRE |
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