Induction of cell senescence by targeting to Cullin-RING Ligases (CRLs) for effective cancer therapy |
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Authors: | Yongfu Pan Hua Xu Rujiao Liu Lijun Jia |
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Affiliation: | 1.Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China;2.Biotherapy Research Center of Fudan University, Shanghai 200032, China |
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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. |
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Keywords: | CRLs senescence RBX1/ROC1 Skp2 cullin neddylation MLN4924 |
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