HIF1‐regulated ATRIP expression is required for hypoxia induced ATR activation
Copyright policy )HIF1‐regulated ATRIP expression is required for hypoxia induced ATR activation
The ATR–ATRIP protein kinase complex plays a crucial role in the cellular response to replication stress and DNA damage. Recent studies found that ATR could be activated in response to hypoxia and be involved in hypoxia‐induced genetic instability in cancer cells. However, the underlying mechanisms for ATR activation in response to hypoxic stress are still not fully understood. We reported that ATRIP is a direct target of HIF‐1. Silencing the expression of HIF‐1α in cancer cells by RNA interference abolished hypoxia‐induced ATRIP expression. Silencing the expression of ATRIP by RNA interference abolished hypoxia induced ATR activation and CHK1 phosphorylation in cancer cells. Taken together, these data shed novel insights on the mechanism of hypoxia‐induced activation of the ATR pathway.
- RENJI HOSPITAL SHANGHAI JIAOTONG UNIVERSITY SCHOOL OF MEDICINE China (People's Republic of)
- Translational Research Institute Australia
- Shanghai Jiao Tong University China (People's Republic of)
Chromatin Immunoprecipitation, Blotting, Western, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Cell Line, ATRIP, Neoplasms, Humans, Phosphorylation, Hypoxia, Promoter Regions, Genetic, Adaptor Proteins, Signal Transducing, Binding Sites, HIF-1, Hep G2 Cells, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, ATR, HEK293 Cells, Checkpoint Kinase 1, MCF-7 Cells, HeLa Cells
Chromatin Immunoprecipitation, Blotting, Western, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Cell Line, ATRIP, Neoplasms, Humans, Phosphorylation, Hypoxia, Promoter Regions, Genetic, Adaptor Proteins, Signal Transducing, Binding Sites, HIF-1, Hep G2 Cells, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, ATR, HEK293 Cells, Checkpoint Kinase 1, MCF-7 Cells, HeLa Cells
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