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Updated: Jan 21, 2026
In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
SCF-FBXO31 E3 ubiquitin ligase in cancer: Molecular insights and clinical implications
Osheen Sahay1, Abhayananda Behera2, Chandra Biswas3
1Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Abstract:
F-box only protein 31 (FBXO31), a substrate adapter of SKP1-Cullin1-F-box (SCF) E3 ubiquitin ligase, was first identified as a candidate tumor suppressor in breast cancer due to its role in inducing senescence. Over the past two decades, FBXO31 has emerged as a crucial regulator in several human cancers, where it promotes the proteasomal degradation of various oncoproteins. FBXO31 plays a crucial role in regulating the cell cycle to maintain genomic integrity and inhibits processes such as epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. This review examines the molecular mechanisms underlying the potent tumor-suppressive functions of FBXO31 in diverse human cancers. We also discuss the underlying causes of FBXO31 deregulation in cancer, providing insights into the intricate regulatory networks governing its expression. Additionally, we also examine the unexpected oncogenic functions of FBXO31 in certain cellular contexts. Finally, we highlight the clinical potential of FBXO31 in human malignancies, discussing its implications as both a biomarker and a therapeutic target. In conclusion, understanding the nuanced biology of FBXO31 is crucial for unravelling its role in tumorigenesis and advancing future therapeutic strategies.
Insights
F-box only protein 31 (FBXO31) acts as a tumor suppressor by degrading oncoproteins and maintaining genomic integrity. Its complex roles in cancer, including potential oncogenic functions, offer new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- F-box only protein 31 (FBXO31) is a key component of the SCF E3 ubiquitin ligase complex.
- Initially identified for its tumor-suppressive role in breast cancer via senescence induction.
- FBXO31 regulates oncoprotein degradation, cell cycle, and epithelial-to-mesenchymal transition (EMT).
Purpose of the Study:
- To review the molecular mechanisms of FBXO31's tumor-suppressive functions across various cancers.
- To explore causes of FBXO31 deregulation and its regulatory networks in cancer.
- To discuss FBXO31's dual role, including unexpected oncogenic functions, and its clinical potential.
Main Methods:
- Literature review of studies on FBXO31 in human cancers.
- Analysis of molecular mechanisms regulating FBXO31 expression and function.
- Examination of clinical data related to FBXO31 as a biomarker and therapeutic target.
Main Results:
- FBXO31 suppresses tumors by degrading oncoproteins, maintaining genomic integrity, and inhibiting metastasis.
- FBXO31 expression is frequently deregulated in cancers.
- FBXO31 exhibits context-dependent oncogenic functions in specific cellular settings.
Conclusions:
- FBXO31 possesses potent tumor-suppressive activities but can also act oncogenically.
- Understanding FBXO31's multifaceted biology is critical for cancer therapy.
- FBXO31 holds promise as a biomarker and therapeutic target in human malignancies.
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