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.
Ruzzene
Maria
M
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo, 3-35121 Padova, Italy.
Penzo
Daniele
D
Pinna
Lorenzo A
LA
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D001798:Blood Proteins / Q000096:biosynthesis*; D047390:Casein Kinase II; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002470:Cell Survival; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
C405354:4,5,6,7-tetrabromobenzotriazole; D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; C061909:HCLS1 protein, human; D014230:Triazoles; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D005047:Etoposide; D011065:Poly(ADP-ribose) Polymerases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases