Calcineurin subunit B promotes TNF-alpha-induced apoptosis by binding to mitochondria and causing mitochondrial Ca2+ overload.
Previous studies have shown that excess calcineurin subunit B (CnB) associates with mitochondria. Here, CnB overexpression increased CN activity in cells and enhanced TNF-alpha-induced cell death independent of CN activity. Overexpression of CnB increased intracellular Ca2+ concentration, enhanced caspase-3 activity, reduced Bcl-2 expression, and decreased mitochondrial membrane potential, with no change of caspase-8 or p53. CnB bound to isolated mitochondria in a Ca(2+)-dependent manner, and stimulated cytochrome c release from the mitochondria. Altogether, these results demonstrate that CnB is capable of promoting TNF-alpha-induced apoptosis, possibly through effects on mitochondrial functions.
Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.
Jinbo
J
Cheng
Wei
W
Tang
Zhenyi
Z
Su
Junxia
J
Guo
Li
L
Tong
Qun
Q
Wei
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000096:biosynthesis; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002352:Carrier Proteins; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c; D019703:Calcineurin; D020169:Caspases; D002118:Calcium