Amino acid starvation sensitizes cancer cells to proteasome inhibition

Sarit Mizrachy-Schwartz*, Noam Cohen, Shoshana Klein, Nataly Kravchenko-Balasha, Alexander Levitzki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


We explored the crosstalk between protein degradation and synthesis in cancer cells. The tumorigenic cell line, MCF7, showed enhanced proteasome activity compared to the nontumorigenic line, MCF10A. Although there was no difference in the sensitivity of MCF7 and MCF10A cells to proteasome inhibition in complete growth medium, combining proteasome inhibition with amino acid deprivation led to reduced protein synthesis and survival of MCF7 cells, with a lesser effect on MCF10A cells. Additional cancer cell lines (including CAG and A431) could be strongly sensitized to proteasome inhibition by concomitant amino acid deprivation, whereas others were completely resistant to proteasome inhibition. We hypothesize that protein catabolism contributes to the pool of free amino acids available for protein synthesis, leading to a crucial role of the proteasome in cell survival during amino acid depletion, in some tumor cell lines.

Original languageAmerican English
Pages (from-to)757-763
Number of pages7
JournalIUBMB Life
Issue number10
StatePublished - Oct 2010


  • amino acid
  • bortezomib
  • cancer
  • proteasome
  • protein synthesis
  • starvation


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