| Autor: |
Fan Sun, Gutian Xiao, Zhaoxia Qu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell & Bioscience, Vol 14, Iss 1, Pp 1-6 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2045-3701 |
| DOI: |
10.1186/s13578-024-01281-x |
| Popis: |
Abstract The PDZ-LIM domain-containing protein PDLIM2 is a common tumor suppressor and a key immune modulator. One main function of PDLIM2 is to promote the ubiquitination and proteasomal degradation of nuclear activated NF-κB RelA, a physiologically indispensable transcription factor whose persistent activation has been linked to almost all cancer types and inflammation-associated diseases. However, it remains unknown how PDLIM2 exerts this physiologically and pathogenically important function. Here, we show that PDLIM2 acts as a ubiquitin ligase enhancer, termed E5. It stabilizes ROC1, an essential component of SKP1/Cullin/F-box protein (SCF) ubiquitin ligases, and chaperones the ROC1-SCFβ-TrCP ubiquitin ligase to ubiquitinate nuclear RelA for proteasomal degradation in the nucleus. Consistently, silencing of ROC1, Cullin 1 or the F-box protein β-TrCP blocks RelA ubiquitination and degradation by PDLIM2. These data provide new mechanistic insights into how PDLIM2 promotes nuclear RelA ubiquitination and degradation, thereby serving as a critical tumor suppressor and a vital immune regulator. They also improve our understanding of the complex cascade of the ubiquitination and NF-κB pathways, particularly given the well-known role of the ROC1-SCFβ-TrCP ubiquitin ligase in initiating NF-κB activation by directly binding to and ubiquitinating NF-κB inhibitors for the proteasomal degradation in the cytoplasm. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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