نتایج جستجو برای: keywords: chk2
تعداد نتایج: 1978979 فیلتر نتایج به سال:
abstract accumulation of gene changes and chromosomal instability in response to cellular dna damage lead to cancer. dna damage induces cell cycle checkpoints pathways. checkpoints regulate dna replication and cell cycle progression, chromatin restructuring, and apoptosis. checkpoint kinase 2 (chk2) is activated in response to dna lesions. atm phosphorylate chk2. the activated chk2 kinase can p...
Accumulation of gene changes and chromosomal instability in response to cellular DNA damage lead to cancer. DNA damage induces cell cycle checkpoints pathways. Checkpoints regulate DNA replication and cell cycle progression, chromatin restructuring, and apoptosis. Checkpoint kinase 2 (chk2) is activated in response to DNA lesions. ATM phosphorylate chk2. The activated Chk2 kinase can phosphoryl...
In response to ionizing radiation, checkpoint kinase 2 (Chk2) is activated in an ataxia telangiectasia mutation-dependent manner and induces either cell cycle arrest or apoptosis. Chk2 is also autophosphorylated following DNA damage. It is proposed that autophosphorylation of Chk2 may contribute to Chk2 activation. To fully understand the regulation of Chk2, we mapped an in vitro Chk2 autophosp...
In response to ionizing radiation (IR), the tumor suppressor p53 is stabilized and promotes either cell cycle arrest or apoptosis. Chk2 activated by IR contributes to this stabilization, possibly by direct phosphorylation. Like p53, Chk2 is mutated in patients with Li-Fraumeni syndrome. Since the ataxia telangiectasia mutated (ATM) gene is required for IR-induced activation of Chk2, it has been...
Chk2 is a protein kinase intermediary in DNA damage checkpoint pathways. DNA damage induces phosphorylation of Chk2 at multiple sites concomitant with activation. Chk2 phosphorylated at Thr-68 is found in nuclear foci at sites of DNA damage (1). We report here that Chk2 phosphorylated at Thr-68 and Thr-26 or Ser-28 is localized to centrosomes and midbodies in the absence of DNA damage. In a sea...
High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated Chk2 then phosphorylates downstream substrates of cell cycle control. However, ...
The Chk2 kinase is a tumor suppressor and key transducer of DNA-damage checkpoints. We show that the human Chk2 protein is relatively stable, nuclear, and responding to gamma-radiation throughout the cell cycle. Contrary to the retinoblastoma protein-regulated, labile Chk1 kinase restricted to S-G(2) phases, Chk2 remains activatable even in quiescent and differentiating cells. In human tissues,...
Checkpoint kinase 2 (Chk2), a DNA damage-activated protein kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites. Using mass spectrometry we identified a new Chk2 phosphorylation site at Ser-456. We show that phosphorylation of Ser-456 plays a role in the regulation of Chk2 stability particularly after DNA d...
The Chk2 protein kinase protects genome integrity by promoting cell cycle arrest or apoptosis in response to DNA double-strand breaks, and Chk2 mutations are found in both familial and sporadic cancers. Exposure of cells to ionizing radiation (IR) or radiomimetic drugs induces Chk2 phosphorylation by ATM, followed by Chk2 oligomerization, auto-/transphosphorylation, and activation. Here we demo...
Chk2 is a checkpoint kinase involved in the ataxia telangiectasia mutated pathway, which is activated by genomic instability and DNA damage, leading to either cell death (apoptosis) or cell cycle arrest. Chk2 provides an unexplored therapeutic target against cancer cells. We recently reported 4,4'-diacetyldiphenylurea-bis(guanylhydrazone) (NSC 109555) as a novel chemotype Chk2 inhibitor. We hav...
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