Diverse Roles of F-BoxProtein3 in Regulation of Various Cellular Functions

Abstract

Accumulated evidence shows that the F-box protein 3 (FBXO3) has multiple biological functions, including regulation of immune pathologies, neuropathic diseases and antiviral response. In this review article, we focus on the role of FBXO3 in inflammatory disorders and human malignancies. We also describe the substrates of FBXO3, which contribute to inflammatory disorders and cancers. We highlight that the high expression of FBXO3 is frequently observed in rheumatoid arthritis, leukemia, pituitary adenoma, and oral squamous cell carcinoma. Moreover, we discuss the regulation of FBXO3 by both carcinogens and cancer preventive agents. Our review provides a comprehensive understanding of the role of FBXO3 in various biological systems and elucidates how FBXO3 regulates substrate ubiquitination and degradation during various physiological and pathological processes. Therefore, FBXO3 can be a novel target in the treatment of human diseases including carcinomas.

Distinct regions within SAP25 recruit O-linked glycosylation, DNA demethylation, and ubiquitin ligase and hydrolase activities to the Sin3/HDAC complex

“…1A). These proteins have previously been shown to regulate gene transcription (12, 16, 28, 29). The observation of OGT with SAP25 is also consistent with several investigations that suggest that Sin3 complex, SAP25, OGT, and TET family proteins (TET1, TET2, and TET3) collaborate in regulating transcription (12, 14, 16, 30).…”

“…1A). Among these, we found that SAP25 captures components of the E3 ubiquitin ligase SCF(FBXO3), which promotes ubiquitination (29). SCF(FBXO3) is built from the substrate recognition protein FBXO3, the adaptor protein SKP1, the cullin CUL1, and a small (12 kDa) ring-box protein RBX1 (29).…”

miR‐219a‐5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3

“…Interestingly, we probed that miR‐219a‐5p exerted its protective effect on KOA by reducing FBXO3 via binding to the 3′ UTR region. FBXO3 possesses multiple biological functions, such as antiviral response and regulation of neuropathic diseases 24 . However, its function in osteoarthritis is still rarely uncovered.…”

“…A review study has been suggested that FBXO3 is highly expressed in the synovial tissues of rheumatoid arthritis. According to the function of FBXO3 regulating the cell cycle, the review study speculates that FBXO3 may modulate rheumatoid arthritis progression by regulating the proliferation as well as survival of rheumatoid arthritis synovial fibroblast 24 . Additionally, it has been suggested that the inhibitor of FBXO3 can diminish the release of IL‐18 as well as IL‐1β in human inflammatory cells through a series of complex processes 25 .…”

“…FBXO3 possesses multiple biological functions, such as antiviral response and regulation of neuropathic diseases. 24 However, its function in osteoarthritis is still rarely uncovered. A review study has been suggested that FBXO3 is highly expressed in the synovial tissues of…”