F-box only protein 9 and its role in cancer

Hussain, Shujaat; Dong, Jianshu; Ma, Xiaofeng; Li, Jian; Shen, Chen; Clement, Agboybor; Liu, Hong‐Min

doi:10.1007/s11033-021-07057-7

Cited by 8 publications

(10 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, magnolol reverses degradation and ubiquitination levels of PPARγ conferred by FBXO9, suggesting that magnolol stabilizes PPARγ by interrupting the interaction of PPARγ and FBXO9. FBXO9, a member of the F-box protein family and a substrate recognition component of the S-phase kinase associated protein 1 (Skp1)-cullin-1-F-box (SCF) E3 ligase complex, has been reported to participate in several cellular processes [37][38][39]. FBXO9 plays a pivotal role in the proteasome-dependent degradation of its substrates, including F-box/WD repeat-containing protein 7 (FBXW7) [38], cellular tumor antigen p53 [39], and PPARγ [15].…”

Section: Discussionmentioning

confidence: 99%

Targeting peroxisome proliferator‐activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis‐mediated metabolic homeostasis

Mei

Wang

et al. 2023

Obesity

View full text Add to dashboard Cite

Objective Adipogenesis has been recognized as an attractive avenue for maintaining systemic homeostasis, with peroxisome proliferator‐activated receptor γ (PPARγ) showing predominant roles in this process. This study aims to identify promising drug candidates by targeting PPARγ for adipogenesis‐based metabolic homeostasis and to clarify the detailed mechanisms. Methods Molecular events contributing to adipogenesis were screened, which identified PPARγ as having the predominant role. Promising agents of adipogenesis agonism were screened using a PPARγ‐based luciferase reporter assay. The functional capacity and molecular mechanisms of magnolol were intensively examined using 3T3‐L1 preadipocytes and dietary models. Results This study found that F‐box only protein 9 (FBXO9)‐mediated lysine 11 (K11)‐linked ubiquitination and proteasomal degradation of PPARγ are critically required during adipogenesis and systemic homeostasis. Notably, magnolol was identified as a potent adipogenesis activator by stabilizing PPARγ. The pharmacological mechanisms investigations clarified that magnolol directly binds to PPARγ and markedly interrupts its interaction with FBXO9, leading to a decline in K11‐linked ubiquitination and proteasomal degradation of PPARγ. Clinically important, magnolol treatment significantly facilitates adipogenesis in vitro and in vivo. Conclusions The downregulation of K11‐linked ubiquitination of PPARγ caused by FBOX9 is essentially required for adipogenesis, while targeting PPARγ‐FBXO9 interaction provides a new avenue for the therapy of adipogenesis‐related metabolic disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting peroxisome proliferator‐activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis‐mediated metabolic homeostasis

Mei

Wang

et al. 2023

Obesity

View full text Add to dashboard Cite

show abstract

“…In recent years, F-box proteins have been identified as essential factors for malignancies via target degradation ( 12 , 28 ). FBXO9 is a mysterious member of the F-box protein family ( 16 ), and a few available studies have shown that FBXO9 is involved in the development of the nervous system or adipose tissue ( 17 , 18 ), in pathological changes in the muscle in diabetes ( 17 ) and epithelial damage in respiratory distress syndrome ( 18 ), and in the adverse effects of zoledronic acid ( 19 ) or as a target of sepsis ( 18 ), and participates in disease progression in hematological tumors by regulating the activity of the mTOR pathway ( 20 ) and the proteasome ( 8 ). However, the biological functions and mechanisms underlying the role of FBXO9 in HCC have not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…For example, FBXL1 promotes tumorigenesis by facilitating the degradation of a series of tumor-suppressor proteins, such as such as p21 and p27 (12); FBXO22 degrades nuclear PTEN to promote tumorigenesis (10); and FBXW7 plays a tumorsuppressive role by degrading various cancer-promoting proteins such as mTOR, cyclin E, MCL-1, N-Myc, and SOX9 (12,14,15). However, less attention has been paid to FBXO9 (16). To date, several substrates of FBXO9 have been identified, including Neurog2 (17), PRMT4 (18), p53 (19), PPARg, BK channel b1 subunit, TEL2, and TTI1 (17,20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma

et al. 2022

View full text Add to dashboard Cite

F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mechanism of FBXO9 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that FBXO9 was remarkably overexpressed in HCC. Loss- and gain-of-function experiments showed that FBXO9 facilitates HCC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, as a direct upstream transcription factor, FBXO9 is regulated by zinc finger protein 143 (ZNF143) and accelerates tumor growth and metastasis by targeting the F-box and WD repeat domain containing 7 (FBXW7) for ubiquitination and degradation. Additionally, we found that with FBXO9 knockdown, HCC cells were more sensitive to treatment with lenvatinib and sorafenib. In summary, our results demonstrate that a ZNF143-FBXO9-FBXW7 signaling regulatory axis may be involved in tumor progression in HCC, and suggest that FBXO9 could be a potential biomarker and therapeutic target for HCC.

show abstract

“…Although the F-box proteins have been recognized to play an important role in cell proliferation and tumor generation [ 26 – 28 ], the function of FBXL16 in endometrial carcinoma is virtually unknown. Compared to other F-box proteins, FBXL16 may have distinct functions since it does not form a stable ligase complex [ 10 – 12 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

FBXL16 Promotes Endometrial Progesterone Resistance via PP2AB55α/Cyclin D1 Axis in Ishikawa

Liu

Li²,

Zhong

et al. 2022

Journal of Immunology Research

View full text Add to dashboard Cite

Background. F-box proteins are essential components of the E3 ubiquitin ligases which are involved in the regulation of almost all life activities such as cell cycle, proliferation, and apoptosis, which have become an important research and drug target. However, there are few studies on F-box and leucine-rich repeat protein 16 (FBXL16) in endometrial carcinoma. Methods. Clinical samples were collected for determining the correlation between FBXL16 and endometrial carcinoma. Cells were screened and established with Ishikawa cells which proved the fundamental role of FBXL16 in regulating cell proliferation and cell cycle. The MPA-resistant endometrial carcinoma cell line Ishikawa/MPA was established. FBXL16, PP2AB55α, and cyclin D1 were analyzed separately in MPA sensitive and resistant Ishikawa cells in vitro and in vivo. Results. The high expression of FBXL16 was positively correlated with MPA resistance and poor prognosis of endometrial cancer. MPA tolerance of endometrial cancer cells was inhibited by knockdown of FBXL16 in DNA content assessment, CCK-8, and colony formation. It was confirmed that FBXL16 inhibited the activity of substrate PP2AB55α by binding to PP2A, reduced the phosphorylation level at Thr308 site of AKT1, inhibited the expression of GSK-3β, and thus led to a significant decrease in the phosphorylation level of cyclin D1, which prevented the ubiquitination recognition and degradation of cyclin D1. Conclusion. In our experiments, FBXL16 binds PP2A to promote the dephosphorylation of Thr286 site of cyclin D1 via AKT1/GSK3β/cyclin D1 pathway, which is required for resisting the ubiquitination degradation and enhances the MPA resistance of Ishikawa.

show abstract

F-box only protein 9 and its role in cancer

Cited by 8 publications

References 80 publications

Targeting peroxisome proliferator‐activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis‐mediated metabolic homeostasis

Targeting peroxisome proliferator‐activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis‐mediated metabolic homeostasis

FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma

FBXL16 Promotes Endometrial Progesterone Resistance via PP2AB55α/Cyclin D1 Axis in Ishikawa

Contact Info

Product

Resources

About