Inhibition of drug-induced Fas ligand transcription and apoptosis by Bcl-XL

R. S. Biswas, H. J. Cha, J. M. Hardwick, R. K. Srivastava

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Fas/Fas ligand system triggers apoptosis in many cell types. Bcl-XL overexpresion antagonizes Fas/Fas ligand-mediated cell death. The mechanism by which Bcl-XL influences Fas-mediated cell death is unclear. We have found that microtubule-damaging drugs (e.g. Paclitaxel) induce apoptosis in a Fas/FasL-dependent manner. Inhibition of Fas/FasL pathway by anti-FasL antibody, mutant Fas or a dominant negative FADD blocks paclitaxel-induced apoptosis. Paclitaxel induced apoptosis through activation of both caspase-8 and caspase-3. Overexpression of Bcl-XL leads to inhibition of paclitaxel-induced FasL expression and apoptosis. Bcl-XL prevents the nuclear translocation of NFAT (nuclear factor of activated T lymphocytes) by inhibiting the activation of calcineurin, a calcium-dependent phosphatase that must dephosphorylate NFAT for it to move to the nucleus. The loop domain in Bcl-XL can suppress the anti-apoptotic function of Bcl-XL and may be a target for regulatory post-translational modifications. Upon phosphorylation, Bcl-XL loses its ability to bind with calcineurin. Without NFAT nuclear translocation, the FasL gene is not transcribed. Thus, paclitaxel and other drugs that disturb microtubule function kill cells, at least in part, through the induction of FasL, and Bcl-XL-mediated resistance to these agents is related to failure to induce FasL expression.

Original languageEnglish (US)
Pages (from-to)7-20
Number of pages14
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - 2001


  • Apoptosis
  • Bcl-X
  • Calcineurin
  • FasL
  • NFAT
  • Paclitaxel

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Inhibition of drug-induced Fas ligand transcription and apoptosis by Bcl-XL'. Together they form a unique fingerprint.

Cite this