FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1
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Curated by eLife
eLife assessment
The paper provides important insight into the function of FAM76B protein as a regulator of inflammation. The knockout/overexpression data are solid, however, the mechanism of regulation and the role of FAM76B in neurodegeneration is incomplete and requires additional experimentation. The work will be of interest to researchers studying inflammation, particularly neuroinflammation.
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Abstract
FAM76B has been reported to be a nuclear speckle-localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediated neuroinflammation via influencing the translocation of hnRNPA2B1 in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.
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eLife assessment
The paper provides important insight into the function of FAM76B protein as a regulator of inflammation. The knockout/overexpression data are solid, however, the mechanism of regulation and the role of FAM76B in neurodegeneration is incomplete and requires additional experimentation. The work will be of interest to researchers studying inflammation, particularly neuroinflammation.
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Reviewer #1 (Public Review):
The first defined that FAM76B inhibited the NF-κB-mediated inflammation by modulating translocation of hnRNPA2B1 to cytosol, where hnRNPA2B1 bound to IKK and released active NFkB that translocated into nuclear and initiated inflammation.
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Reviewer #2 (Public Review):
This manuscript describes a study of a novel role of FAM76B in regulation of NF-kB-mediated inflammation, specially in neuroinflammation both in animal model and human brain disease. This study was logically designed and laid out and data from gene knockdown and knockout cell line and animals strongly support the note that FAM76B is involved in the neuroinflammatory diseases. This notion was further confirmed in patients with brain inflammatory diseases. Importantly, the authors further dissected the cellular molecular action of FAM76B in regulation of NF-kB pathway through binding to the hnRNPA2B1. However, it is still unclear how the FAM76B regulates/or affects the cytoplasmic translocation of hnRNPA2B1 in brain cells after a variety of inflammatory stimuli or injuries. Nonetheless, this study greatly …
Reviewer #2 (Public Review):
This manuscript describes a study of a novel role of FAM76B in regulation of NF-kB-mediated inflammation, specially in neuroinflammation both in animal model and human brain disease. This study was logically designed and laid out and data from gene knockdown and knockout cell line and animals strongly support the note that FAM76B is involved in the neuroinflammatory diseases. This notion was further confirmed in patients with brain inflammatory diseases. Importantly, the authors further dissected the cellular molecular action of FAM76B in regulation of NF-kB pathway through binding to the hnRNPA2B1. However, it is still unclear how the FAM76B regulates/or affects the cytoplasmic translocation of hnRNPA2B1 in brain cells after a variety of inflammatory stimuli or injuries. Nonetheless, this study greatly enhances our understanding of the mechanisms of the brain inflammation and inflammation related brain degeneration.
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