Radiosensitization by Chir-124, a selective Chk1 inhibitor: Effects of p53 and cell cycle checkpoints
نویسندگان
چکیده
منابع مشابه
PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints.
The ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) kinases respond to DNA damage by phosphorylating cellular target proteins that activate DNA repair pathways and cell cycle checkpoints in order to maintain genomic integrity. Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1...
متن کاملCHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo.
PURPOSE Chk1 kinase is a critical regulator of both S and G(2)-M phase cell cycle checkpoints in response to DNA damage. This study aimed to evaluate the biochemical, cellular, and antitumor effects of a novel Chk1 inhibitor, CHIR124. EXPERIMENTAL DESIGN CHIR-124 was evaluated for its ability to abrogate cell cycle checkpoints, to potentiate cytotoxicity, and to inhibit Chk1-mediated signalin...
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Two cell cycle surveillance systems--the DNA damage checkpoint and the spindle checkpoint--guard against genomic instability. The protein kinase Chk1 is a well-established signal transducer in the DNA damage checkpoint. In this issue of Developmental Cell, Zachos et al.(2007) present evidence to indicate that Chk1 also plays a critical role in the spindle checkpoint, suggesting an interplay bet...
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Cell cycle checkpoints are surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle. These include growth to the appropriate cell size, the replication and integrity of the chromosomes, and their accurate segregation at mitosis. Many of these mechanisms are ancient in origin and highly conserved, and hence have been heavily informed by studie...
متن کاملCyclins and cell cycle checkpoints.
The eucaryotic cell cycle is regulated by the periodic synthesis and destruction of cyclins that associate with and activate cyclin-dependent kinases. Cyclin-dependent kinase inhibitors, such as p21 and p16, also play important roles in cell cycle control by coordinating internal and external signals and impeding proliferation at several key checkpoints. Understanding how these proteins interac...
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ژورنال
عنوان ژورنال: Cell Cycle
سال: 2009
ISSN: 1538-4101,1551-4005
DOI: 10.4161/cc.8.8.8203