FBXW2

Last update 08 May 2025

Basic Info

Synonyms

F-box and WD repeat domain containing 2, F-box and WD-40 domain-containing protein 2, F-box/WD repeat-containing protein 2

+ [5]

Introduction

Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

100 Clinical Results associated with FBXW2

100 Translational Medicine associated with FBXW2

0 Patents (Medical) associated with FBXW2

Literatures (Medical) associated with FBXW2

24 Mar 2025·International Journal of Medical Sciences

FBXW2 inhibits the progression of gastric cancer via promoting β-catenin ubiquitylation

Article

Author: Ke, Mu ; Liu, Weizheng ; Xu, Fengming ; Kuang, Yanshen

Background: F-box and WD-repeat-containing protein 2 (FBXW2), an E3 ubiquitin ligase, may play a crucial role in tumorigenesis. However, its function in gastric cancer remains unknown. Methods: The expression levels of FBXW2 and β-catenin in gastric cancer samples were analyzed using RT-PCR and immunohistochemistry, with Pearson correlation analysis to assess their relationship. AGS and HGC-27 gastric cancer cells were transfected with sh-FBXW2, and their viability was evaluated using the CCK8 assay, while invasion ability was assessed via the transwell assay. Western blotting was performed to measure the expression levels of FBXW2, β-catenin, GSK3β, and Axin2 in AGS cells. Additionally, a ubiquitination assay was conducted to examine the effect of sh-FBXW2 on β-catenin ubiquitination. Immunoprecipitation was used to determine the potential interaction between FBXW2 and β-catenin. Results: FBXW2 expression was downregulated, whereas β-catenin expression was upregulated in gastric cancer tissues compared to adjacent normal tissues, showing a significant negative correlation (r = -0.52, P < 0.001). Knockdown of FBXW2 (sh-FBXW2) promoted gastric cancer cell viability and invasion while increasing β-catenin expression and reducing GSK3β and Axin2 levels. Furthermore, FBXW2 was found to bind β-catenin and facilitate its ubiquitination, leading to enhanced nuclear translocation of β-catenin. Conclusions: FBXW2 suppresses gastric cancer progression by promoting β-catenin ubiquitination, highlighting its potential as a therapeutic target.

01 Jul 2024·American Journal of Respiratory Cell and Molecular Biology

Activated Clec4n^hi Neutrophils Aggravate Lung Injury in an Endothelial IGFBP7-Dependent Manner

Article

Author: Qi, Di ; He, Rui ; Wang, Dao-Xin ; Yu, Lin-Chao

The role of endothelial cells in acute lung injury (ALI) has been widely elaborated, but little is known about the role of different subtypes of endothelial cells in ALI. ALI models were established by lipopolysaccharide. Single-cell RNA sequencing was used to identify differential molecules in endothelial subtypes and the heterogeneity of lung immune cells. Specific antibodies were used to block insulin-like growth factor binding protein 7 (IGFBP7), and AAV_shIGP7 was used to specifically knock down IGFBP7. Here, we found that IGFBP7 was the most differentially expressed molecule in diverse subsets of endothelial cells and that IGFBP7 was strongly associated with inflammatory responses. Elevated IGFBP7 significantly exacerbated barrier dysfunction in ALI, whereas blockade of IGFBP7 partially reversed barrier damage. General capillary cells are the primary source of elevated serum IGFBP7 after ALI. Using single-cell RNA sequencing, we identified significantly increased Clec4n^hi neutrophils in mice with ALI, whereas IGFBP7 knockdown significantly reduced infiltration of Clec4n^hi cells and mitigated barrier dysfunction in ALI. In addition, we found that IGFBP7 activated the NF-κB signaling axis by promoting phosphorylation and ubiquitination degradation of F-box/WD repeat-containing protein 2 (FBXW2), thereby exacerbating barrier dysfunction in ALI. Taken together, our data indicate that blockade of serum IGFBP7 or IGFBP7 depletion in general capillary cells reversed barrier damage in ALI. Therefore, targeting IGFBP7 depletion could be a novel strategy for treating ALI.

01 Mar 2024·Free Radical Biology and Medicine

Reduced mitochondrial-encoded NADH dehydrogenase 6 gene expression drives inflammatory CD4+T cells in patients with systemic lupus erythematosus

Article

Author: Abdukiyum, Miheraiy ; Huang, Mengxi ; Yu, Honghong ; Zheng, Yuanyuan ; Tang, Xiaojun ; Cui, Yiyuan ; Li, Wenjing ; Alim, Tohtihan ; Zhang, Jingjing ; Feng, Xuxue ; Zhao, Nan ; Feng, Xuebing

Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m⁶A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4⁺ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial indicators in CD4⁺ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4⁺ T cells.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

FBXW2

Basic Info

Related

Analysis