FBXW7 Confers Radiation Survival by Targeting p53 for Degradation
Danrui Cui, Xiufang Xiong, Jianfeng Shu, Xiao-Qing Dai, Yi Sun, Yongchao Zhao
Abstract
by small molecular inhibitors or genetic knockdown/knockout approaches extends the p53 protein half-life upon DNA damage in an MDM2-independent manner. Biologically, FBXW7 inactivation sensitizes cancer cells to radiation or etoposide by stabilizing p53 to induce cell-cycle arrest and apoptosis. Taken together, our study elucidates a mechanism by which FBXW7 confers cancer cell survival during radiotherapy or chemotherapy via p53 targeting.
Topics & Concepts
Ubiquitin ligaseDNA damageUbiquitinMdm2Cancer researchDNA repairCell cycle checkpointCell biologyBiologySuppressorEtoposideGene knockdownApoptosisF-box proteinCell cycleChemistryCancerDNAGeneticsChemotherapyGeneCancer-related Molecular PathwaysUbiquitin and proteasome pathwaysCancer, Hypoxia, and Metabolism