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 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.
Jeong
Eui Man
EM
Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea.
Kim
Chai-Wan
CW
Cho
Sung-Yup
SY
Jang
Gi-Yong
GY
Shin
Dong-Myung
DM
Jeon
Ju-Hong
JH
Kim
In-Gyu
IG
D000256:Adenoviridae / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000166:cytology; D007976:Leupeptins / Q000494:pharmacology; D018384:Oxidative Stress; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013997:Time Factors; D011503:Transglutaminases / Q000378:metabolism*; D054875:Ubiquitination
D000900:Anti-Bacterial Agents; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D007976:Leupeptins; D000001:Calcimycin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D002118:Calcium