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Fbxw8 is involved in the proliferation of human prostate cancercells

Ping Lin  Feng Lin  Xiulan Zheng  Haifeng Zou  Hui Chen  Rongjun Cui  Jiebing Tang  Xiaoguang Yu  
【摘要】:Background: Ubiquitin–proteasome pathway plays indispensable roles in many biologicalprocesses. The protein ubiquitination is catalyzed by three enzymes, the E1 ubiquitin activatingenzyme, the E2 ubiquitin conjugating enzymes, and the E3 ubiquitin ligases. TheSkp1–CUL1–F-box(SCF) multi-subunit complex is a well characterized E3 ligase, Skp1 canalso form an E3 complex with CUL7, Rbx1, and F-box and WD repeat domain containing 8(Fbxw8), which is the only known F-box protein in CUL7 E3 complex. Fbxw8 has been involvedin the proteasomal degradation of insulin receptor substrate 1(IRS-1), and it also plays an essential role in the proliferation of colon cancer cells via proteolysis of cyclin D1.In the present study, we evaluated the effects of Fbxw8 on the proliferation and on the cellcycle distribution of human prostate cancer cells. Results: We firstly examined the expression levels of Fbxw8 in six human prostate cancer cell lines, and we found the expression of Fbxw8 is much higher in DU145 cells compare to PC-3 cells. Knock-down Fbxw8 by siRNA significantly inhibited DU145 cells proliferation and the G2/M transition in cell cycle,which is mediated by down-regulation of CDK1, CDK2, cyclin A and cyclin B1 at protein level in association with induction of p27. Stable over-expression of Fbxw8 induced PC-3cells proliferation and G2/M cell cycle transition through up-regulation of CDK1, CDK2,cyclin A and cyclin B1 and down regulation of p27. Conclusions: In summary, Fbxw8 regulated cell proliferation and promoted cell cycle progression, which may be achieved by increasing the expressions of CDK1, CDK2, cyclin A and cyclin B1 as well as decreasing the expressions of P27. We also showed that Fbxw8 might be a potential target for prostate cancer prevention and therapy.

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1 Ping Lin;Feng Lin;Xiulan Zheng;Haifeng Zou;Hui Chen;Rongjun Cui;Jiebing Tang;Xiaoguang Yu;;Fbxw8 is involved in the proliferation of human prostate cancercells[A];中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议论文集——专题报告三[C];2014年
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