Publication Date:
2008-11-22
Description:
Why do seemingly identical cells respond differently to a drug? To address this, we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution. All cells show rapid translocation of proteins specific to the drug mechanism, including the drug target (topoisomerase-1), and slower, wide-ranging temporal waves of protein degradation and accumulation. However, the cells differ in the behavior of a subset of proteins. We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes-cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, A A -- Geva-Zatorsky, N -- Eden, E -- Frenkel-Morgenstern, M -- Issaeva, I -- Sigal, A -- Milo, R -- Cohen-Saidon, C -- Liron, Y -- Kam, Z -- Cohen, L -- Danon, T -- Perzov, N -- Alon, U -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1511-6. doi: 10.1126/science.1160165. Epub 2008 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. ariel.cohen@weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19023046" target="_blank"〉PubMed〈/a〉
Keywords:
Antineoplastic Agents, Phytogenic/*pharmacology
;
Camptothecin/*pharmacology
;
Cell Death
;
Cell Division/drug effects
;
Cell Line, Tumor
;
Cell Nucleolus/drug effects/metabolism
;
Cell Nucleus/drug effects/metabolism
;
Cell Survival/drug effects
;
Cytoplasm/drug effects/metabolism
;
DEAD-box RNA Helicases/metabolism
;
DNA Damage
;
DNA Topoisomerases, Type I/*metabolism
;
Enzyme Inhibitors/pharmacology
;
Fluorescence
;
Humans
;
Luminescent Proteins/metabolism
;
Lung Neoplasms/*metabolism/*pathology
;
Metabolic Networks and Pathways
;
Oxidative Stress
;
Proteins/*metabolism
;
Proteome/*metabolism
;
Proteomics
;
Replication Protein C/metabolism
;
Topoisomerase I Inhibitors
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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