The interleukin 1beta-converting enzyme inhibitor CrmA prevents Apo1/Fas- but not glucocorticoid-induced poly(ADP-ribose) polymerase cleavage and apoptosis in lymphoblastic leukemia cells

FEBS Lett. 1997 Jan 27;402(1):36-40. doi: 10.1016/s0014-5793(96)01496-2.


Glucocorticoids (GC) induce programmed cell death (apoptosis) in immature lymphocytes and are an essential component in the therapy of acute lymphatic leukemia. The mechanism underlying GC-induced apoptosis particularly in leukemia cells is, however, not well understood. Most forms of apoptosis seem to employ a common final effector pathway characterized by specific proteolytic events mediated by interleukin 1beta-converting enzyme (ICE) and/or other ICE-like cysteine proteases. These events may result in the morphologic changes characteristic of apoptosis. To determine whether a similar proteolytic pathway is activated during GC-induced leukemia cell apoptosis, we investigated poly(ADP-ribose) polymerase (PARP), a typical target of ICE-like proteases, during GC-induced apoptosis of the human acute T-cell leukemic cell line CEM-C7H2. Our studies showed proteolytic PARP cleavage suggestive of activation of ICE-like proteases that preceeded morphologic signs of apoptosis. We further established stably transfected CEM-C7H2 sublines expressing the cowpox virus protein CrmA that inhibits some, but not all, ICE-like proteases. GC-induced PARP cleavage and apoptosis were neither inhibited nor delayed in crmA-expressing cell lines. In contrast, crmA expression rendered the same lines resistant to Apo1/Fas-induced PARP cleavage and apoptosis. Thus, different proteases might be activated during the effector phases of GC-and Apo1/Fas-induced apoptosis in human leukemia cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase 1
  • Cysteine Endopeptidases / metabolism*
  • Dexamethasone / pharmacology*
  • Glucocorticoids / pharmacology*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / enzymology
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Serpins / genetics
  • Serpins / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Viral Proteins*
  • fas Receptor / immunology
  • fas Receptor / physiology


  • Glucocorticoids
  • Serpins
  • Viral Proteins
  • fas Receptor
  • Poly Adenosine Diphosphate Ribose
  • Dexamethasone
  • interleukin-1beta-converting enzyme inhibitor
  • Cysteine Endopeptidases
  • Caspase 1