SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration

Dong, Shuying; Wei, Jianxin; Bowser, Rachel K.; Chen, Bill B.; Mallampalli, Rama K.; Miao, Jr‐Ming; Ye, Qinmao; Tran, Kevin; Zhao, Yutong; Zhao, Jing

doi:10.1002/jcb.29860

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…Because overexpression of FBXL19 or PDLIM2 suppresses RANKL in osteocytic cells, preventing the reduction of FBXL19 and PDLIM2 proteins or increasing the stability of these ubiquitin ligases will be a strategy for suppressing RANKL in osteocytes. FBXL19 degradation is regulated by FBXW17-mediated ubiquitination and CBP-mediated acetylation 67 , 68 . Manipulating these mechanisms of FBXL19 degradation may be an approach to suppress osteoclastogenesis in bone infection.…”

Section: Discussionmentioning

confidence: 99%

Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection

et al. 2022

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The impact of bone cell activation on bacterially-induced osteolysis remains elusive. Here, we show that matrix-embedded osteocytes stimulated with bacterial pathogen-associated molecular patterns (PAMPs) directly drive bone resorption through an MYD88-regulated signaling pathway. Mice lacking MYD88, primarily in osteocytes, protect against osteolysis caused by calvarial injections of bacterial PAMPs and resist alveolar bone resorption induced by oral Porphyromonas gingivalis (Pg) infection. In contrast, mice with targeted MYD88 restoration in osteocytes exhibit osteolysis with inflammatory cell infiltration. In vitro, bacterial PAMPs induce significantly higher expression of the cytokine RANKL in osteocytes than osteoblasts. Mechanistically, activation of the osteocyte MYD88 pathway up-regulates RANKL by increasing binding of the transcription factors CREB and STAT3 to Rankl enhancers and by suppressing K48-ubiquitination of CREB/CREB binding protein and STAT3. Systemic administration of an MYD88 inhibitor prevents jawbone loss in Pg-driven periodontitis. These findings reveal that osteocytes directly regulate inflammatory osteolysis in bone infection, suggesting that MYD88 and downstream RANKL regulators in osteocytes are therapeutic targets for osteolysis in periodontitis and osteomyelitis.

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Section: Discussionmentioning

confidence: 99%

Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection

et al. 2022

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“…A recent research showed that FBXW17 ubiquitinates FBXL19 for its degradation. Silence of FBXW17 attenuated lysophosphatidic acid (LPA)-induced epithelial cell migration (Dong et al, 2020), which suggested a potential role of FBXW17 in cell function regulation. Small molecules inhibiting FBXO3 reduce cytokine release and lessen associated inflammatory diseases via destabilizing tumor necrosis factor receptor-associated factor (TRAF) protein (Chen et al, 2013;Mallampalli et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

“…FBXW17, an ortholog of FBXW12 in mouse genome, is a 466-amino-acid protein containing an F-box motif for the recognition of substrate and the recruitment of ubiquitylation (Jin et al, 2004). As an SCF protein member, FBXW17 has a similar sequence to other FBPs, which is recently reported to ubiquitinate FBXL19 for its degradation (Dong et al, 2020). However, its function and other molecular targets remain to be determined further depending on its role in SCF subunits.…”

Section: Introductionmentioning

confidence: 99%

F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis

Luo

et al. 2021

Front. Cell Dev. Biol.

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Chronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent inflammation and epithelial apoptosis induced by cigarette smoke would be extremely beneficial for improving the treatment and prevention of COPD. A histone methyl modifier, protein arginine N-methyltransferase 6 (PRMT6), is reported to alleviate cigarette smoke extract (CSE)-induced emphysema through inhibiting inflammation and cell apoptosis. However, few studies have focused on the modulation of PRMT6 in regulating inflammation and cell apoptosis. In this study, we showed that protein expression of PRMT6 was aberrantly decreased in the lung tissue of COPD patients and CSE-treated epithelial cells. FBXW17, a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases, selectively bound to PRMT6 in nuclei to modulate its elimination in the proteasome system. Proteasome inhibitor or silencing of FBXW17 abrogated CSE-induced PRMT6 protein degradation. Furthermore, negative alteration of FBXW17/PRMT6 signaling lessened the proapoptotic and proinflammatory effects of CSE in lung epithelial cells. Our study, therefore, provides a potential therapeutic target against the airway inflammation and cell death in CS-induced COPD.

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“…Retinoblastoma (RB), a malignant tumor derived from photoreceptor precursor cells, is usually found in children under 3 years old, with family genetic predisposition. Circ-0075804 promotes RB cell proliferation by binding to heterogeneous ribonucleoprotein K (HNRNPK), thereby increasing the stability of E2F3 mRNA, which indicates that circ-0075804 may become a therapeutic target for RB patients [ 39 ]. Xu found that circVAPA was upregulated in human RB specimens and RB cell lines through qRT-PCR, and was associated with the poor prognosis of RB patients.…”

Section: Circrna and Common Smts In Childrenmentioning

confidence: 99%

The emerging role of circular RNAs in common solid malignant tumors in children

Yang

2021

Cancer Cell Int

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Malignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.

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SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration

Cited by 6 publications

References 41 publications

Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection

Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection

F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis

The emerging role of circular RNAs in common solid malignant tumors in children

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