Bak interacts with AKT and is involved in TNFα/CHX-induced apoptosis

Mol Cell Biochem. 2022 Mar;477(3):939-949. doi: 10.1007/s11010-021-04348-2. Epub 2022 Jan 30.

Abstract

Bak is important for TNFα/CHX-induced neuronal death, but the precise molecular mechanism remains unclear. At the same time, TNFα/CHX concomitantly activates the phosphorylation of the MAPK and PI3K/AKT kinases. This study for the first time clarified the association between the MAPK and AKT under the TNFα/CHX stimulation upon addition of different kinase inhibitors to show whether Bak is associated with the kinase activation. The bioinformatics software HDOCK predicted the interaction between Bak and AKT. The addition of TNFα/CHX was proposed to destroy the complex, such that the dissociated Bak would exert a proapoptosis effect AKT can influence the inhibition of cell apoptosis. There was no cell death upon inducing TNFα/CHX for 3 h. AKT was less obvious with apoptosis but in the Bak knockout cells, the anti-apoptotic effect of AKT was very obvious. This study, therefore, provides the theoretical basis for the molecular mechanism of apoptosis induced by TNFα/CHX, providing a new target and direction for studying drug resistance.

Keywords: AKT; Apoptosis; Bak; CHX; TNFα.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cycloheximide / pharmacology*
  • Humans
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*

Substances

  • BAK1 protein, human
  • Tumor Necrosis Factor-alpha
  • bcl-2 Homologous Antagonist-Killer Protein
  • Cycloheximide
  • Proto-Oncogene Proteins c-akt