Proteasomes Modulate Balance Among Proapoptotic and Antiapoptotic Bcl-2 Family Members and Compromise Functioning of the Electron Transport Chain in Leukemic Cells | Zendy

Vladimir Marshansky | Zendy; Xin Wang | Zendy; Richard Bertrand | Zendy; Hongyu Luo | Zendy; William P. Duguid | Zendy; G. Chinnadurai | Zendy; Nada Kanaan | Zendy; Minh Diem Vu | Zendy; Jiangping Wu | Zendy

Open Access

Proteasomes Modulate Balance Among Proapoptotic and Antiapoptotic Bcl-2 Family Members and Compromise Functioning of the Electron Transport Chain in Leukemic Cells

Author(s) -

Vladimir Marshansky,

Xin Wang,

Richard Bertrand,

Hongyu Luo,

William P. Duguid,

G. Chinnadurai,

Nada Kanaan,

Minh Diem Vu,

Jiangping Wu

Publication year - 2001

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.166.5.3130

Subject(s) - lactacystin , apoptosis , cytochrome c , proteasome , mitochondrion , bcl xl , bcl 2 family , microbiology and biotechnology , jurkat cells , apoptosome , intrinsic apoptosis , programmed cell death , proteasome inhibitor , mitochondrial apoptosis induced channel , biology , chemistry , caspase , biochemistry , immunology , t cell , immune system

The mechanism underlying apoptosis induced by proteasome inhibition in leukemic Jurkat and Namalwa cells was investigated in this study. The proteasome inhibitor lactacystin differentially regulated the protein levels of proapoptotic Bcl-2 family members and Bik was accumulated at the mitochondria. Bik overexpression sufficed to induce apoptosis in these cells. Detailed examination along the respiration chain showed that lactacystin compromised a step after complex III, and exogenous cytochrome c could overcome this compromise. Probably as a result, the succinate-stimulated generation of mitochondrial membrane potential was significantly diminished. Bcl-x(L) interacted with Bik in the cells, and Bcl-x(L) overexpression prevented cytochrome c leakage out of the mitochondria, corrected the mitochondrial membrane potential defect, and protected the cells from apoptosis. These results show that proteasomes can modulate apoptosis of lymphocytes by affecting the half-life of Bcl-2 family members, Bik being one of them.

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