NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR

作     者：Yuzu Zhao Jiang He Yongsen Li Shengqing Lv Hongjuan Cui Yuzu Zhao;Jiang He;Yongsen Li;Shengqing Lv;Hongjuan Cui

作者机构：State Key Laboratory of Silkworm Genome BiologySouthwest UniversityChongqingChina Cancer CenterMedical Research InstituteSouthwest UniversityChongqingChina Department of NeurosurgeryXinqiao HospitalThird Military Medical UniversityChongqingChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2020年第5卷第1期

页      面：2019-2029页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China(Nos.2016YFC1302204, 2017YFC1308601) the Natural Science Foundation of China(Nos.81872071,81672502) the Fundamental Research Funds for the Central Universities(XDJK2018D003) the Graduate Scientific Research Foundation of Chongqing(CYB18102) 

主　　题：AP1 damage ATR 

摘      要：NUSAP1,which is a microtubule-associated protein involved in mitosis,plays essential roles in diverse biological processes,especially in cancer *** this study,NUSAP1 was found to be overexpressed in GBM tissues in a grade-dependent manner compared with normal brain ***1 was also highly expressed in GBM patients,dead patients,and GBM *** addition,NUSAP1 was found to participate in cell proliferation,apoptosis,and DNA damage in GBM *** telangiectasia and Rad3-related protein(ATR)are a primary sensor of DNA damage,and ATR is also a promising target in cancer ***,we found that NUSAP1 positively regulated the expression of ***,NUSAP1 suppressed the ubiquitin-dependent proteolysis of *** SAP(SAF-A/B,Acinus,and PIAS)domain is a common motif of many SUMO(small ubiquitin-like modifier)E3 ligases,and this domain is involved in substrate recognition and ligase *** study further demonstrated that the SAP domain of NUSAP1 promoted the sumoylation of ATR,and thereby antagonized the ubiquitination of *** results suggest that NUSAP1 stabilizes ATR by ***,NUSAP1 potentiated chemotherapeutic resistance to temozolomide(TMZ)and doxorubicin(DOX)through its SAP ***,this study indicates that NUSAP1 is a promising therapeutic target in GBM.