# FBXW10

## Overview
FBXW10 is a gene that encodes the protein F-box and WD repeat domain containing 10, which is a member of the F-box protein family. This protein is characterized by the presence of an F-box motif, which is crucial for its role in the ubiquitin-proteasome system, a pathway responsible for protein degradation. As part of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, the protein encoded by FBXW10 is involved in tagging specific proteins for ubiquitination, thereby regulating protein turnover and maintaining cellular homeostasis (Feng2013FBXW10). The protein also plays a role in chromatin organization by targeting heterochromatin proteins for degradation (Chaturvedi2010Lamin). FBXW10's involvement in cellular processes such as protein synthesis, degradation, and signal transduction highlights its importance in maintaining cellular regulation and stability (Feng2013FBXW10).

## Function
FBXW10 is a member of the F-box protein family, which plays a crucial role in the ubiquitin-proteasome system, a pathway responsible for protein degradation. It is part of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which tags proteins for degradation, thereby regulating protein turnover and maintaining cellular homeostasis (Feng2013FBXW10). In healthy human cells, FBXW10 is involved in targeting specific proteins for ubiquitination, a process essential for controlling protein synthesis and degradation, impacting cell cycle progression and signal transduction (Feng2013FBXW10).

FBXW10 is also implicated in the regulation of ubiquitination-related genes through protein O-GlcNAcylation, a dynamic modification process. It is negatively regulated at both the mRNA and protein levels in response to increased protein O-GlcNAcylation, suggesting a role in the cross-talk between O-GlcNAcylation and ubiquitination (Feng2013FBXW10). Additionally, FBXW10 is involved in the degradation of heterochromatin proteins HP1α and HP1β, which are targeted for proteasomal degradation, indicating its role in chromatin organization and stability (Chaturvedi2010Lamin). The specific function of FBXW10 in healthy cells remains to be fully elucidated, but it is clear that it plays a significant role in protein homeostasis and cellular regulation.

## Clinical Significance
FBXW10 has been implicated in several cancers due to alterations in its expression and methylation status. In clear cell renal cell carcinoma (ccRCC), FBXW10 is hypermethylated, particularly in higher Fuhrman grades of stage T1 tumors. This hypermethylation correlates with more aggressive disease characteristics, suggesting that FBXW10 methylation could serve as a biomarker for ccRCC diagnosis and treatment strategies (WANG2015Abnormal). 

In hepatocellular carcinoma (HCC), FBXW10 is highly expressed and associated with poor prognosis, especially in male patients. It promotes fibrosis, inflammation, and vascular invasion, contributing to tumor progression. Studies using FBXW10 transgenic mice have shown increased susceptibility to liver fibrosis and tumorigenesis, indicating its role as a potential prognostic marker for HCC in males (Luo2019FBXW10).

FBXW10 is also negatively regulated by protein O-GlcNAcylation, which affects its expression at both mRNA and protein levels. This regulation suggests a link between O-GlcNAcylation and FBXW10's role in cellular processes, although the specific clinical implications of this interaction are not fully detailed (Feng2013FBXW10).


## References


[1. (Chaturvedi2010Lamin) Pankaj Chaturvedi and Veena K. Parnaik. Lamin a rod domain mutants target heterochromatin protein 1α and β for proteasomal degradation by activation of f-box protein, fbxw10. PLoS ONE, 5(5):e10620, May 2010. URL: http://dx.doi.org/10.1371/journal.pone.0010620, doi:10.1371/journal.pone.0010620. This article has 40 citations and is from a peer-reviewed journal.](https://doi.org/10.1371/journal.pone.0010620)

[2. (WANG2015Abnormal) JINYOU WANG, JIAN LI, JUN GU, JIAN YU, SHICHENG GUO, YAO ZHU, and DINGWEI YE. Abnormal methylation status of fbxw10 and smpd3, and associations with clinical characteristics in clear cell renal cell carcinoma. Oncology Letters, 10(5):3073–3080, September 2015. URL: http://dx.doi.org/10.3892/ol.2015.3707, doi:10.3892/ol.2015.3707. This article has 22 citations and is from a peer-reviewed journal.](https://doi.org/10.3892/ol.2015.3707)

[3. (Feng2013FBXW10) Zhou Feng, Yan Hui, Li Ling, Liu Xiaoyan, Wang Yuqiu, Wang Peng, and Zhang Lianwen. Fbxw10 is negatively regulated in transcription and expression level by protein o-glcnacylation. Biochemical and Biophysical Research Communications, 438(2):427–432, August 2013. URL: http://dx.doi.org/10.1016/j.bbrc.2013.07.091, doi:10.1016/j.bbrc.2013.07.091. This article has 10 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.bbrc.2013.07.091)

[4. (Luo2019FBXW10) Yuan-Deng Luo, Jie Zhang, Lei Fang, Yan-Yin Zhu, Yue-Mei You, Cheng-Cheng Zhang, Ping Zheng, Lei-Da Zhang, Liang-Yu Yin, Feng Xia, Ping Bie, and Chuan-Ming Xie. Fbxw10 promotes hepatocarcinogenesis in male patients and mice. Carcinogenesis, 41(5):689–698, August 2019. URL: http://dx.doi.org/10.1093/carcin/bgz138, doi:10.1093/carcin/bgz138. This article has 11 citations and is from a peer-reviewed journal.](https://doi.org/10.1093/carcin/bgz138)