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Published on: October 10, 2017
Negative regulation of RelA phosphorylation: emerging players and their roles in cancer
Xinyuan Lu1, Wendell G Yarbrough2
1Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA; Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
Abstract:
NF-κB signaling contributes to human disease processes, notably inflammatory diseases and cancer. Many advances have been made in understanding mechanisms responsible for abnormal NF-κB activation with RelA post-translational modification, particularly phosphorylation, proven to be critical for RelA function. While the majority of studies have focused on identifying kinases responsible for NF-κB phosphorylation and pathway activation, recently progress has also been made in understanding the negative regulators important for restraining RelA activity. Here we summarize negative regulators of RelA phosphorylation, their targeting sites in RelA and biological functions through negative regulation of RelA activation. Finally, we emphasize the tumor suppressor-like roles that these negative regulators can assume in human cancers.
Insights
Negative regulators of RelA phosphorylation restrain its activity, acting as tumor suppressors in human cancers. Understanding these negative regulators is crucial for targeting NF-κB signaling in disease.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Oncology
Background:
- Nuclear factor-kappa B (NF-κB) signaling is implicated in inflammatory diseases and cancer.
- RelA phosphorylation is a key post-translational modification regulating NF-κB activity.
- While kinases activating NF-κB are well-studied, negative regulators are gaining attention.
Purpose of the Study:
- To summarize the known negative regulators of RelA phosphorylation.
- To detail their specific targeting sites on RelA.
- To elucidate their biological functions in restraining NF-κB activation and their roles in cancer.
Main Methods:
- Literature review and synthesis of existing research on NF-κB negative regulators.
- Analysis of studies focusing on RelA phosphorylation sites and their functional consequences.
- Examination of data linking negative regulators to tumor suppression.
Main Results:
- Several negative regulators of RelA phosphorylation have been identified.
- These regulators target specific phosphorylation sites on RelA, inhibiting its activity.
- These negative regulators exhibit tumor suppressor-like functions in human cancers.
Conclusions:
- Negative regulators of RelA phosphorylation are critical for controlling NF-κB pathway activation.
- These regulators play significant roles in preventing uncontrolled cell proliferation and cancer development.
- Targeting these negative regulators could offer novel therapeutic strategies for cancer treatment.
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