Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Apoptosis*
-
Blood Proteins / biosynthesis*
-
Casein Kinase II
-
Caspase 3
-
Caspases / metabolism*
-
Cell Death
-
Cell Survival
-
Cytochrome c Group / metabolism
-
DNA Fragmentation
-
Dose-Response Relationship, Drug
-
Enzyme Inhibitors / pharmacology*
-
Etoposide / pharmacology
-
Humans
-
Jurkat Cells
-
Phosphorylation
-
Poly(ADP-ribose) Polymerases / metabolism
-
Precipitin Tests
-
Protein Binding
-
Protein Serine-Threonine Kinases / antagonists & inhibitors*
-
Protein Serine-Threonine Kinases / metabolism
-
Serine / metabolism
-
Threonine / metabolism
-
Time Factors
-
Triazoles / pharmacology*
-
Tyrosine / metabolism
Substances
-
4,5,6,7-tetrabromobenzotriazole
-
Adaptor Proteins, Signal Transducing
-
Blood Proteins
-
Cytochrome c Group
-
Enzyme Inhibitors
-
HCLS1 protein, human
-
Triazoles
-
Threonine
-
Tyrosine
-
Serine
-
Etoposide
-
Poly(ADP-ribose) Polymerases
-
Casein Kinase II
-
Protein Serine-Threonine Kinases
-
CASP3 protein, human
-
Caspase 3
-
Caspases