Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation.

Hui Liu,Yang Yang,Hui Wang,Chunlei Guo,Lin Zeng

doi:10.3389/fimmu.2022.847699

Abstract

The NF-κB transcription factor family controls the transcription of many genes and regulates a number of pivotal biological processes. Its activity is regulated by the IκB family of proteins. Bcl-3 is an atypical member of the IκB protein family that regulates the activity of nuclear factor NF-κB. It can promote or inhibit the expression of NF-κB target genes according to the received cell type and stimulation, impacting various cell functions, such as proliferation and differentiation, induction of apoptosis and immune response. Bcl-3 is also regarded as an environment-dependent cell response regulator that has dual roles in the development of B cells and the differentiation, survival and proliferation of Th cells. Moreover, it also showed a contradictory role in inflammation. At present, in addition to the work aimed at studying the molecular mechanism of Bcl-3, an increasing number of studies have focused on the effects of Bcl-3 on inflammation, immunity and malignant tumors in vivo. In this review, we focus on the latest progress of Bcl-3 in the regulation of the NF-κB pathway and its extensive physiological role in inflammation and immune cells, which may help to provide new ideas and targets for the early diagnosis or targeted treatment of various inflammatory diseases, immunodeficiency diseases and malignant tumors.

Highlights

The mammalian nuclear factor kappa B (NF-kB) is a transcription factor of eukaryotic cells and contains several proteins including p65 (RelA), c-Rel, RelB, p50 and p52
The regulation mechanism is as follows: In terms of transcriptional inhibition, studies by Kerr et al confirmed that B-cell lymphoma factor 3 (Bcl-3) protein produced in bacteria could suppress the DNA binding activity of some NF-kB members [9]
The findings indicate that Bcl-3 may play a key role in T3-induced hepatocyte proliferation (Figure 2)

Summary

Introduction

The mammalian nuclear factor kappa B (NF-kB) is a transcription factor of eukaryotic cells and contains several proteins including p65 (RelA), c-Rel, RelB, p50 and p52. The regulation mechanism is as follows: In terms of transcriptional inhibition, studies by Kerr et al confirmed that Bcl-3 protein produced in bacteria could suppress the DNA binding activity of some NF-kB members [9]. It binds to p50 and p52 NF-kB homodimers in the nucleus and activates transcription via the transactivation domain of Bcl-3, leading to abundant cell gene expression and cell proliferation [55].

Results

Conclusion