The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells

@article{Johnson2003ThePI,
  title={The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells},
  author={Thomas R. Johnson and Kimberley Clawson Stone and Malti Nikrad and Tammie C Yeh and Wei-Xing Zong and Craig B Thompson and Alexandre Nesterov and Andrew S. Kraft},
  journal={Oncogene},
  year={2003},
  volume={22},
  pages={4953-4963}
}
We demonstrate that PS-341, a small molecule inhibitor of the proteasome, markedly sensitizes resistant prostate, colon, and bladder cancer cells to TNF-like apoptosis-inducing ligand (TRAIL)-induced apoptosis irrespective of Bcl-xL overexpression. PS-341 treatment by itself does not affect the levels of Bax, Bak, caspases 3 and 8, c-Flip or FADD, but elevates levels of TRAIL receptors DR4 and DR5. This increase in receptor protein levels is associated with the ubiquitination of the DR5 protein… CONTINUE READING