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

Biochem J. 2002 May 15;364(Pt 1):41-7. doi: 10.1042/bj3640041.

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

  • 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
  • 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