FBX8 degrades GSTP1 through ubiquitination to suppress colorectal cancer progression
FBX8 degrades GSTP1 through ubiquitination to suppress colorectal cancer progression
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FBX8 通过泛素化降解 GSTP1 以抑制结直肠癌进展
DOI：
10.1038/s41419-019-1588-z
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发表时间：
2019-04-25
影响因子：
9
通讯作者：
Liang Li
中科院分区：
文献类型：
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作者：
Wang FeiFei;Xu HongHai;Liang Li
F-box only蛋白8（F-box only protein 8，FBX 8）是SKP 1-CUL 1-F-box（SCF）E3泛素连接酶的重要组成部分，通过与蛋白质的相互作用与多种恶性肿瘤相关。然而，FBX 8在结直肠癌（CRC）进展中的破坏底物需要探索。在这里，我们发现FBX 8的丢失加速了化学诱导的结肠肿瘤发生。FBX 8直接靶向GST P1，用于CRC中泛素介导的蛋白酶体降解。GST P1促进CRC细胞的增殖、侵袭和转移。此外，GST P1在CRC组织样品中上调，并预测CRC患者的不良预后。FBX 8的失活与临床CRC组织和FBX 8敲除转基因小鼠中GSTP 1水平和稳定性的增加呈负相关。这些发现确定了一种新的泛素化途径，即调控CRC进展的FBX 8-GSTP 1轴，这可能是CRC患者的潜在预后生物标志物。
F-box only protein 8 (FBX8), as a critical component of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases, has been associated with several malignancies through interacting with a member of proteins. However, the substrates of FBX8 for destruction in the progression of colorectal carcinoma (CRC) need to be explored. Here, we show that loss of FBX8 accelerates chemical-induced colon tumorigenesis. FBX8 directly targets GSTP1 for ubiquitin-mediated proteasome degradation in CRC. GSTP1 promotes the proliferation, invasion, and metastasis of CRC cells. Furthermore, GSTP1 is upregulated in CRC tissue samples and predicts poor prognosis of CRC patients. The inactivation of FBX8 negatively correlated with increased levels and stability of GSTP1 in clinical CRC tissues and FBX8 knockout transgenic mice. These findings identify a novel ubiquitination pathway as FBX8-GSTP1 axis that regulates the progression of CRC, which might be a potential prognostic biomarker for CRC patients.