Int J Biochem Mol Biol 2012;3(3):273-281
Review Article
Induction of cell senescence by targeting to Cullin-RING Ligases (CRLs) for effective
cancer therapy
Yongfu Pan, Hua Xu, Rujiao Liu, Lijun Jia
Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2Biotherapy Research Center of Fudan
University, Shanghai, 200032,China
Received July 22, 2012; Accepted September 17, 2012; Epub September 25, 2012; Published September 30, 2012
Abstract: Cullin-RING ligases (CRLs) are the biggest family of multiunit ubiquitin E3 ligases, controlling many biological processes by
promoting the degradation of a broad spectrum of proteins associated with cell cycle, signal transduction and cell growth. The dysfunction of
CRLs causes a lot of diseases including cancer, which meanwhile offers us a promising approach to cancer therapy by targeting to CRLs.
Recent studies have demonstrated that genetic or pharmaceutical inactivation of CRLs often leads to cancer cell death by activating multiple
cell-killing pathways including senescence, an emerging anticancer mechanism of therapeutic agents. Here, we summarize the induction of
cellular senescence and its mechanism of action, triggered by targeting to specific subunits of CRLs via multiple approaches including siRNA
silencing, genetic knockout as well as small molecule inhibitor, exhibiting anticancer effect in vitro and in vivo. (IJBMB1207002).
Keywords: CRLs, senescence, RBX1/ROC1, Skp2, cullin neddylation, MLN4924
Address all correspondence to:
Lijun Jia
Department of Immunology
Shanghai Medical College, Fudan University
Shanghai 200032, China.
Tel: 86-21-54237751
E-mail: jialijun2002@yahoo.com.cn
Review Article
Induction of cell senescence by targeting to Cullin-RING Ligases (CRLs) for effective
cancer therapy
Yongfu Pan, Hua Xu, Rujiao Liu, Lijun Jia
Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2Biotherapy Research Center of Fudan
University, Shanghai, 200032,China
Received July 22, 2012; Accepted September 17, 2012; Epub September 25, 2012; Published September 30, 2012
Abstract: Cullin-RING ligases (CRLs) are the biggest family of multiunit ubiquitin E3 ligases, controlling many biological processes by
promoting the degradation of a broad spectrum of proteins associated with cell cycle, signal transduction and cell growth. The dysfunction of
CRLs causes a lot of diseases including cancer, which meanwhile offers us a promising approach to cancer therapy by targeting to CRLs.
Recent studies have demonstrated that genetic or pharmaceutical inactivation of CRLs often leads to cancer cell death by activating multiple
cell-killing pathways including senescence, an emerging anticancer mechanism of therapeutic agents. Here, we summarize the induction of
cellular senescence and its mechanism of action, triggered by targeting to specific subunits of CRLs via multiple approaches including siRNA
silencing, genetic knockout as well as small molecule inhibitor, exhibiting anticancer effect in vitro and in vivo. (IJBMB1207002).
Keywords: CRLs, senescence, RBX1/ROC1, Skp2, cullin neddylation, MLN4924
Address all correspondence to:
Lijun Jia
Department of Immunology
Shanghai Medical College, Fudan University
Shanghai 200032, China.
Tel: 86-21-54237751
E-mail: jialijun2002@yahoo.com.cn
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