Abstract
NF-κB is a ubiquitously expressed transcription factor that regulates a large number of genes in response to diverse physiological and pathological stimuli. The regulation of the transcriptional activity of NF-κB is often dependent on its interaction with IκBα. Proteins that bind to IκBα are critical regulators of NF-κB activity. DDRGK1 is a member of the DDRGK domain-containing protein family with unknown function. In this study, we showed that the depletion of DDRGK1 inhibits cell proliferation and invasion. Microarray analysis indicated that the expression of NF-κB target genes showed the most significant decrease after depleting of DDRGK1, suggesting that DDRGK1 may play an important role in the NF-κB signaling pathway. We further demonstrated that DDRGK1 interacts with IκBα and regulates its stability, thereby regulates the NF-κB transcriptional activity. Our findings identify DDRGK1 as an important regulator of the NF-κB pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Cell Line
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Cell Movement / genetics
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Cell Proliferation
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Cluster Analysis
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Gene Expression Profiling
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Gene Expression Regulation
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Humans
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I-kappa B Proteins / metabolism*
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism*
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Protein Binding
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Protein Stability
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Proteins / genetics
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Proteins / metabolism*
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RNA Interference
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Transcriptional Activation
Substances
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Adaptor Proteins, Signal Transducing
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DDRGK1 protein, human
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I-kappa B Proteins
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NF-kappa B
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NFKBIA protein, human
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Proteins
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Cyclin D1
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NF-KappaB Inhibitor alpha
Grants and funding
This work was supported in part by grants from the National Natural Science Foundation of China [31071200, 31171320] and the National Basic Research Program of China [2012CB911203]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.