Search results for "Wee1"

On Cancer Cell Cycle and Universal Apoptosis Parameters Signaling Unravelled In Silico

2010

Here, cell cycle in higher eukaryotes and their molecular networks signals both in G1/S and G2/M transitions are in silico replicated. Systems control theory is employed to design multi-nestled digital layers to simulate protein-to- protein activation and inhibition in the cancer cell cycle dynamics in presence of damaged genome. Sequencing and controlling the digital process of four micro-scale species networks (p53/Mdm2/DNA damage; p21mRNA/cyclin-CDK complex; CDK/CDC25/wee1/SKP2/APC/CKI and apoptosis target genes system) paved the way for unravelling the participants and their by-products having the task to execute (or not) cell death. The results of the proposed cell digital multi-layers…

Vers la validation fonctionnelle du gène WEE1 dans l’acquisition de la résistance au stress abiotique chez des protéagineux

2017

Sensibilisation aux drogues chimiothérapeutiques des tumeurs P53 négatives par activation de la phosphatase Wip1

2017

P53 is mutated in more than half of human cancers and when inactivated is often associated with a resistance to anti-cancer therapy. Our team has hown that in the case of p53-negative tumors, overexpression of Wip1 phosphatase sensitizes tumor cells to chemotherapy, while protecting normal tissues from the side effects of the treatment. To improve this strategy, two main objectives were studied. Firstly, to find a protein which can interact with Wip1 pathway and potentiate its action in this therapeutic strategy. Secondly, to find a molecule which can activate Wip1. We realized a siRNA screening of the whole human kinome to identify several kinases, whose inhibition could potentiate anti-tu…

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

2016

AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…