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PMID: 11988074 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

The Biochemical journal ·Vol. 364 ·No. Pt 1 ·2002-05-15 ·Pages 41-7

Ruzzene M, Penzo D, Pinna LA

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.

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,metabolism Serine/metabolism Threonine/metabolism Time Factors Triazoles/pharmacology Tyrosine/metabolism
Chemicals
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ruzzene Maria
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo, 3-35121 Padova, Italy.
Penzo Daniele
Pinna Lorenzo A
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3640041
Published
2002-05-15
Pages
41-7
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1222543
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3640041 PMC Full Text View journal details
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