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°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. Cell Death and Differentiation (2001) 8, 210–218
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Abbreviations
- ALLM:
-
Ac-Leucinyl-leucinyl-methional
- E64:
-
trans-epoxysuccinyl-L-leucylamido-3-methyl-butane ethyl ester
- GF:
-
growth factor
- MG132:
-
Cb2-leucinyl-leucinyl-leucinal
- PMSF:
-
phenylmethylsulphonyl fluoride
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MacLaren, A., Chapman, R., Wyllie, A. et al. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. Cell Death Differ 8, 210–218 (2001). https://doi.org/10.1038/sj.cdd.4400801
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DOI: https://doi.org/10.1038/sj.cdd.4400801
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