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Amino acid starvation sensitizes cancer cells to proteasome inhibition
Author(s) -
MizrachySchwartz Sarit,
Cohen Noam,
Klein Shoshana,
KravchenkoBalasha Nataly,
Levitzki Alexander
Publication year - 2010
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.377
Subject(s) - proteasome , amino acid , cell culture , catabolism , proteasome inhibitor , cancer cell , biochemistry , crosstalk , protein degradation , biology , protein biosynthesis , microbiology and biotechnology , chemistry , enzyme , cancer , genetics , physics , optics
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. © 2010 IUBMB IUBMB Life, 62(10): 757–763, 2010