Anticancer-drug-induced apoptotic cell death in leukemia cells is associated with proteolysis of beta-catenin

Leuk Res. 2002 Sep;26(9):863-71. doi: 10.1016/s0145-2126(02)00018-8.


beta-Catenin is a known regulator of cell-cell adhesion and transcriptional regulation. However, the role of beta-catenin and its regulation in non-adherent cells has not been examined. Therefore, we examined the role and fate of beta-catenin during hematopoietic cell apoptosis using Jurkat T-acute lymphoblastic and U937 acute myeloblastic leukemia cells. The results presented here demonstrate that the treatment of Jurkat cells with the apoptosis inducers anti-Fas, TRAIL, staurosporine, and etoposide induces proteolytic fragments of beta-catenin, as did TRAIL and staurosporine in U937 cells. In Jurkat cells, beta-catenin was cleaved at both the N- and C-terminal after anti-Fas addition. Cleavage of intact beta-catenin was completely inhibited by caspase selective protease inhibitors. There was a clear accumulation of the large proteolytic fragment in Jurkat cells treated with lactacystin or N-acetyl-leucyl leucyl-methioninal (ALLM). These results suggest that both the proteasome and calpain may recognize the large beta-catenin fragment as a substrate for further degradation. Densitometric analysis demonstrated that the loss of intact beta-catenin was more rapid in the cell nucleus (beta-catenin T1/2 of approximately 1.5h in cytoplasm and 0.5h in nucleus). Down-regulation of beta-catenin-associated transcription was an early event in response to anti-Fas. These results suggest that beta-catenin plays a role in promoting Jurkat survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Calpain / pharmacology
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytoskeletal Proteins / physiology*
  • Fas Ligand Protein
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Jurkat Cells / drug effects*
  • Jurkat Cells / metabolism
  • Membrane Glycoproteins / physiology
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism*
  • Neoplasm Proteins / physiology*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Proteasome Endopeptidase Complex
  • Recombinant Fusion Proteins / physiology
  • Trans-Activators / physiology*
  • Transcription, Genetic / drug effects
  • Transfection
  • U937 Cells / drug effects*
  • U937 Cells / metabolism
  • beta Catenin
  • fas Receptor / immunology
  • fas Receptor / physiology


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Cysteine Proteinase Inhibitors
  • Cytoskeletal Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • beta Catenin
  • fas Receptor
  • Calpain
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex