Phosphorylation of bid by casein kinases I and II regulates its cleavage by caspase 8

Mol Cell. 2001 Sep;8(3):601-11. doi: 10.1016/s1097-2765(01)00335-5.

Abstract

Bid plays an essential role in Fas-mediated apoptosis of the so-called type II cells. In these cells, following cleavage by caspase 8, the C-terminal fragment of Bid translocates to mitochondria and triggers the release of apoptogenic factors, thereby inducing cell death. Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. When phosphorylated, Bid was insensitive to caspase 8 cleavage in vitro. Moreover, a mutant of Bid that cannot be phosphorylated was found to be more toxic than wild-type Bid. Together, these data indicate that phosphorylation of Bid represents a new mechanism whereby cells control apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Casein Kinase II
  • Casein Kinases
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Cell Fractionation
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Granzymes
  • Humans
  • Immunoblotting
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Protein Kinases / isolation & purification
  • Protein Kinases / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine Endopeptidases / metabolism
  • fas Receptor / metabolism

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Bid protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • fas Receptor
  • Protein Kinases
  • Casein Kinase II
  • Casein Kinases
  • Protein-Serine-Threonine Kinases
  • GZMB protein, human
  • Granzymes
  • Gzmb protein, mouse
  • Serine Endopeptidases
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases