1. Academic Validation
  2. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells

p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells

  • Cell Death Differ. 2001 Mar;8(3):210-8. doi: 10.1038/sj.cdd.4400801.
A P MacLaren 1 R S Chapman A H Wyllie C J Watson
Affiliations

Affiliation

  • 1 Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh, EH2 4XU, UK. A.Maclaren@beatson.gla.ac.uk
Abstract

We have examined the effects of inhibition of the 26S Proteasome in a murine mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132. These studies have demonstrated a clear requirement for Proteasome function in cell viability. Induction of Apoptosis was observed following MG132 treatment in KIM-2 cells and this death was shown to be dependent on the cell actively traversing the cell cycle. KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response. Studies in two additional cell lines, HC11, which is a mammary epithelial cell line carrying mutant p53 alleles and p53 null ES cells suggest that p53 is actively required for the Apoptosis induced as a consequence of Proteasome inhibition. These results suggest a pivotal role for the 26S Proteasome degradation pathway in progression through the cell cycle in proliferating cells.

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