An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.
Accumulating reports demonstrate that apoptosis does not explain all the forms of programmed cell death (PCD), particularly in individual development and neurodegenerative disease. Recently, a novel type of PCD, designated 'paraptosis', was described. Here, we show that overexpression of TAJ/TROY, a member of the tumor necrosis factor receptor superfamily, induces non-apoptotic cell death with paraptosis-like morphology in 293T cells. Transmission electron microscopy studies reveal extensive cytoplasmic vacuolation and mitochondrial swelling in some dying cells and no condensation or fragmentation of the nuclei. Characteristically, cell death triggered by TAJ/TROY was accompanied by phosphatidylserine externalization, loss of the mitochondrial transmembrane potential and independent of caspase activation. In addition, TAJ/TROY suppressed clonogenic growth of HEK293 and HeLa cells. Interestingly, overexpression of Programmed cell death 5 (PDCD5), an apoptosis-promoting protein, enhanced TAJ/TROY-induced paraptotic cell death. Moreover, cellular endogenous PDCD5 protein was significantly upregulated in response to TAJ/TROY overexpression. These results provide novel evidence that TAJ/TROY activates a death pathway distinct from apoptosis and that PDCD5 is an important regulator in both apoptotic and non-apoptotic PCD.
Wang
Ying
Y
Laboratory of Medical Immunology, School of Basic Medical Science, Peking University, Xueyuan Road 38, Beijing 100083, China.
Li
Xianting
X
Wang
Lu
L
Ding
Peiguo
P
Zhang
Yingmei
Y
Han
Wenling
W
Ma
Dalong
D
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D010718:Phosphatidylserines; D018124:Receptors, Tumor Necrosis Factor; C409471:Tnfrsf19 protein, mouse