Details

Autor(en) / Beteiligte

• Zeng, Linlin
• Li, Ting
• Xu, Derek C.
• Liu, Jennifer
• Mao, Guozhang
• Cui, Mei-Zhen
• Fu, Xueqi
• Xu, Xuemin

Titel

Death Receptor 6 Induces Apoptosis Not through Type I or Type II Pathways, but via a Unique Mitochondria-dependent Pathway by Interacting with Bax Protein

Ist Teil von

• The Journal of biological chemistry, 2012-08, Vol.287 (34), p.29125-29133

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced apoptosis. Our results strongly suggest that DR6-induced apoptosis occurs through a new pathway that is different from the type I and type II pathways through interacting with Bax. Background: DR6-induced apoptosis mechanism is unknown. Results: DR6-induced apoptosis is dependent on cytochrome c release and Bax translocation, but is independent of caspase-8 and Bid. Conclusion: DR6-induced apoptosis is mediated by a unique pathway, different from type I and type II pathways. Significance: This study will lead to a better understanding of the mechanism by which DR6 induces apoptosis.