Proteomics

Dataset Information

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MOLT-4 radiosensitization by VE-821


ABSTRACT: DNA damage induction by either radio- or chemo-therapy has been the most widely used approach in cancer therapy, exploiting the genomic instability of cancer cells. A promising strategy takes advantage of tumour specific abnormalities in DNA damage response. Inhibition of the ATR/Chk1 pathway has been shown to be synthetically lethal in cells with high levels of oncogene-induced replication stress and in p53- or ATM- deficient cells. In the presented study, we aimed to elucidate molecular mechanisms underlying radiosensitization of MOLT-4 cells by VE-821, a higly potent and specific inhibitor of ATR. We combined multiple approaches: cell biology techniques to reveal the inhibitor-induced phenotypes, and quantitative proteomics, phosphoproteomics, and metabolomics to comprehensively describe drug-induced changes in irradiated cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, T Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Barbora Salovska  

LAB HEAD: Aleš Tichý

PROVIDER: PXD008925 | Pride | 2018-07-16

REPOSITORIES: Pride

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Publications

Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells.

Šalovská Barbora B   Janečková Hana H   Fabrik Ivo I   Karlíková Radana R   Čecháková Lucie L   Ondrej Martin M   Link Marek M   Friedecký David D   Tichý Aleš A  

PloS one 20180712 7


Current anti-cancer strategy takes advantage of tumour specific abnormalities in DNA damage response to radio- or chemo-therapy. Inhibition of the ATR/Chk1 pathway has been shown to be synthetically lethal in cells with high levels of oncogene-induced replication stress and in p53- or ATM- deficient cells. In the presented study, we aimed to elucidate molecular mechanisms underlying radiosensitization of T-lymphocyte leukemic MOLT-4 cells by VE-821, a higly potent and specific inhibitor of ATR.  ...[more]

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