Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding to high oxidative stress

Transglutaminase 2 (TG2) is a calcium-dependent enzyme that catalyzes the transamidation reaction. There is conflicting evidence on the role of TG2 in apoptosis. In this report, we show that TG2 increases in response to low level of oxidative stress, whereas TG2 diminishes under high stress conditio...

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Bibliographic Details
Published in:FEBS letters 2009-02, Vol.583 (4), p.648-654
Main Authors: Jeong, Eui Man, Kim, Chai-Wan, Cho, Sung-Yup, Jang, Gi-Yong, Shin, Dong-Myung, Jeon, Ju-Hong, Kim, In-Gyu
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Anti-Bacterial Agents - pharmacology
Apoptosis
biotinylated pentylamine
Calcimycin - pharmacology
Calcium - metabolism
Calcium-overload
Cell Death
Cell Line
Culture Media, Serum-Free
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
GTP-Binding Proteins - metabolism
HeLa Cells
hemagglutinin
horseradish peroxidase-conjugated streptavidin
Humans
Kidney - cytology
Leupeptins - pharmacology
Oxidative Stress
Proteasomal degradation
SA-HRP
TG2
Time Factors
Transglutaminase 2
Transglutaminases - metabolism
Ubiquitination
ultra violet
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Summary:Transglutaminase 2 (TG2) is a calcium-dependent enzyme that catalyzes the transamidation reaction. There is conflicting evidence on the role of TG2 in apoptosis. In this report, we show that TG2 increases in response to low level of oxidative stress, whereas TG2 diminishes under high stress conditions. Monitoring TG2 expression, activity and calcium concentration in cells treated with A23187 revealed that the initial rise of calcium activates TG2 but subsequent calcium-overload induces the degradation of TG2 via calcium-mediated polyubiquitination. These results indicate that the role of TG2 in apoptosis depends on the level of calcium influx triggered by oxidative stress. MINT- 6824687: TG2 (uniprotkb: P21980) physically interacts (MI: 0218) with Ubiquitin (uniprotkb: P62988) by anti bait coimmunoprecipitation (MI: 0006)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2009.01.032