The CXXC finger 5 protein is required for DNA damage-induced p53 activation.
The tumor suppressor p53 is a critical component of the DNA damage response pathway that induces a set of genes responsible for cell cycle arrest, senescence, apoptosis, and DNA repair. The ataxia telangiectasia mutated protein kinase (ATM) responds to DNA-damage stimuli and signals p53 stabilization and activation, thereby facilitating transactivation ... of p53 inducible genes and maintainence of genome integrity. In this study, we identified a CXXC zinc finger domain containing protein termed CF5 as a critical component in the DNA damage signaling pathway. CF5 induces p53 transcriptional activity and apoptosis in cells expressing wild type p53 but not in p53-deficient cells. Knockdown of CF5 inhibits DNA damage-induced p53 activation as well as cell cycle arrest. Furthermore, CF5 physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin. These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage.
Mesh Terms:
Amino Acid Sequence, Animals, Antineoplastic Agents, Phytogenic, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA-Binding Proteins, Etoposide, Gene Expression Regulation, Hela Cells, Humans, Molecular Sequence Data, Protein-Serine-Threonine Kinases, RNA Interference, Sequence Alignment, Signal Transduction, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zinc Fingers
Amino Acid Sequence, Animals, Antineoplastic Agents, Phytogenic, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA-Binding Proteins, Etoposide, Gene Expression Regulation, Hela Cells, Humans, Molecular Sequence Data, Protein-Serine-Threonine Kinases, RNA Interference, Sequence Alignment, Signal Transduction, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zinc Fingers
Sci. China, C, Life Sci.
Date: Jun. 01, 2009
PubMed ID: 19557330
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