NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression
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ABSTRACT:
PROVIDER: PRJNA478059 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7430670.fastq.gz | Fastqsanger.gz | |||
| SRR7430680.fastq.gz | Fastqsanger.gz | |||
| SRR7430690.fastq.gz | Fastqsanger.gz | |||
| SRR7430700.fastq.gz | Fastqsanger.gz | |||
| SRR7430671.fastq.gz | Fastqsanger.gz |
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Project description:Post-translational modification of NF-κB subunits provides a mechanism to differentially regulate their activity in response to the many stimuli that can induce this pathway. However, the physiological significance of these modifications is largely unknown and it remains unclear if these have a critical role in the normal and pathological functions of NF-κB in vivo. Among these, phosphorylation of the RelA(p65) Thr505 residue has been described as an important regulator of NF-κB activity in cell lines but its physiological significance was not known. Therefore, to learn more about the role of this pathway in vivo, we generated a knockin mouse with a RelA T505A mutation. Unlike RelA knockout mice, the RelA T505A mice develop normally but exhibit aberrant hepatocyte proliferation following liver partial hepatectomy or damage resulting from carbon tetrachloride treatment. Consistent with these effects, RelA T505A mice exhibit earlier onset of cancer in the N-nitrosodiethylamine (DEN) model of hepatocellular carcinoma. This data reveals a critical pathway controlling NF-κB function in the liver that acts to suppress tumour-promoting activities of RelA.
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