Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer
The NF-κB family of dimeric transcription factors regulate diverse biological functions. Their cellular expression profiles differ, which lead to different concentrations in different cell/tissue types. Although the activation mechanisms of different NF-κB dimers have been widely investigated, there...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.930619/full |
| _version_ | 1811220989850157056 |
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| author | Wenfei Pan Limei Deng Haitao Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang |
| author_facet | Wenfei Pan Limei Deng Haitao Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang |
| author_sort | Wenfei Pan |
| collection | DOAJ |
| description | The NF-κB family of dimeric transcription factors regulate diverse biological functions. Their cellular expression profiles differ, which lead to different concentrations in different cell/tissue types. Although the activation mechanisms of different NF-κB dimers have been widely investigated, there is limited information on specific NF-κB dimers’ formation. The NF-κB p52:p52 homodimer regulates an important subset of target genes in cancer cells; however, the molecular mechanism of the generation of this specific homodimer remains unclear. Our study has revealed that the atypical IκB protein, Bcl3, plays an essential role in enhancing the p52:p52 homodimer population which is a unique mechanism to p52 within the NF-κB family. p52 was shown to heterodimerize with four other NF-κB subunits (RelA, RelB, cRel, and p50); all heterodimers, except p52:p50, are significantly more stable than the p52:p52 homodimer. Bcl3 is able to compete with all other NF-κB subunits in cells for efficient p52:p52 homodimer formation which consequently leads to the upregulation of target genes that are involved in cell proliferation, migration, and inflammation, which explain why aberrant activation of Bcl3 and p52 leads to cancer. |
| first_indexed | 2024-04-12T07:51:14Z |
| format | Article |
| id | doaj.art-7162e5d003804b66a0394f407ad41f0c |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T07:51:14Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-7162e5d003804b66a0394f407ad41f0c2022-12-22T03:41:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.930619930619Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimerWenfei Pan0Limei Deng1Haitao Wang2Vivien Ya-Fan Wang3Vivien Ya-Fan Wang4Vivien Ya-Fan Wang5Faculty of Health Sciences, University of Macau, Avenida da Universidade, Macau SAR, ChinaFaculty of Health Sciences, University of Macau, Avenida da Universidade, Macau SAR, ChinaThoracic Surgery Branch, Clinical Research, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United StatesFaculty of Health Sciences, University of Macau, Avenida da Universidade, Macau SAR, ChinaCancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Macau SAR, ChinaMoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida da Universidade, Macau SAR, ChinaThe NF-κB family of dimeric transcription factors regulate diverse biological functions. Their cellular expression profiles differ, which lead to different concentrations in different cell/tissue types. Although the activation mechanisms of different NF-κB dimers have been widely investigated, there is limited information on specific NF-κB dimers’ formation. The NF-κB p52:p52 homodimer regulates an important subset of target genes in cancer cells; however, the molecular mechanism of the generation of this specific homodimer remains unclear. Our study has revealed that the atypical IκB protein, Bcl3, plays an essential role in enhancing the p52:p52 homodimer population which is a unique mechanism to p52 within the NF-κB family. p52 was shown to heterodimerize with four other NF-κB subunits (RelA, RelB, cRel, and p50); all heterodimers, except p52:p50, are significantly more stable than the p52:p52 homodimer. Bcl3 is able to compete with all other NF-κB subunits in cells for efficient p52:p52 homodimer formation which consequently leads to the upregulation of target genes that are involved in cell proliferation, migration, and inflammation, which explain why aberrant activation of Bcl3 and p52 leads to cancer.https://www.frontiersin.org/articles/10.3389/fcell.2022.930619/fullNF-κB—nuclear factor-kappa BdimerizationBcl3NF-κB:IκB complexgene expression |
| spellingShingle | Wenfei Pan Limei Deng Haitao Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang Vivien Ya-Fan Wang Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer Frontiers in Cell and Developmental Biology NF-κB—nuclear factor-kappa B dimerization Bcl3 NF-κB:IκB complex gene expression |
| title | Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer |
| title_full | Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer |
| title_fullStr | Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer |
| title_full_unstemmed | Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer |
| title_short | Atypical IκB Bcl3 enhances the generation of the NF-κB p52 homodimer |
| title_sort | atypical iκb bcl3 enhances the generation of the nf κb p52 homodimer |
| topic | NF-κB—nuclear factor-kappa B dimerization Bcl3 NF-κB:IκB complex gene expression |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.930619/full |
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