Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells.

Incubation of Jurkat cells with 4,5,6,7-tetrabromobenzotriazole (TBB), a specific inhibitor of protein kinase CK2, induces dose-and time-dependent apoptosis as judged by several criteria. TBB-promoted apoptosis is preceded by inhibition of Ser/Thr phosphorylation of haematopoietic lineage cell-specific protein 1 (HS1) and is accompanied by caspase-dependent fragmentation of the same protein. Both ...
effects are also observable if apoptosis is promoted by anti-Fas antibodies and by etoposide. Moreover, in vitro experiments show that HS1, once phosphorylated by CK2, becomes refractory to cleavage by caspase-3. These findings, in conjunction with similar data in the literature concerning two other CK2 protein substrates, Bid and Max, suggest that CK2 may play a general anti-apoptotic role through the generation of phosphorylated sites conferring resistance to caspase cleavage.
Mesh Terms:
Apoptosis, Blood Proteins, Casein Kinase II, Caspase 3, Caspases, Cell Death, Cell Survival, Cytochrome c Group, DNA Fragmentation, Dose-Response Relationship, Drug, Enzyme Inhibitors, Etoposide, Humans, Jurkat Cells, Phosphorylation, Poly(ADP-ribose) Polymerases, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Serine, Threonine, Time Factors, Triazoles, Tyrosine
Biochem. J.
Date: May. 15, 2002
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