Neddylation pathway promotes the ubiquitinated degradation of FBXO21 in lung cancer cells.

Authors

Ying Zhang, Meng Li, Tiangeng Dong, Yunyang Zhou, Wenjuan Zhang, Gaili Chang, Mingsong Wang, Lijun Jia, Lihui Li

Published in

Carcinogenesis. Volume 47. Issue 3. Jul 07, 2026.

Abstract

SCF (Skp1-Cullin1-Fbox protein) is a multi-subunit RING-type E3 ligase and plays critical roles in various pivotal physiological and pathological processes by mediating the ubiquitination and degradation of key proteins. F-box proteins directly bind substrates, thereby determining their specificity, stability, and function. However, the regulatory mechanisms of FBXO21 degradation in human cancers remain largely elusive. In this study, we demonstrated that Neddylation-ROC1 E3 ligase regulates the protein level of FBXO21. Mechanistic studies revealed that Neddylation-ROC1 targeted FBXO21 for ubiquitination and degradation. Moreover, we found that FBXO21 depletion increased p53 protein stability by delaying its degradation, followed by increasing the transcriptional level of p21. Taken together, our findings reveal a previously unrecognized mechanism by which FBXO21 is regulated by Neddylation modification and regulates the p53-p21 signaling pathway.

PMID:
42555346
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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