NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR
作者： Yuzu Zhao , Jiang He , Yongsen Li , Shengqing Lv , Hongjuan Cui
DOI: 10.1038/S41392-020-0137-7
关键词: Cell biology 、 DNA damage 、 Apoptosis 、 Ligase activity 、 SUMO protein 、 Ataxia-telangiectasia 、 Mitosis 、 Doxorubicin 、 Ubiquitin 、 Chemistry
摘要: NUSAP1, which is a microtubule-associated protein involved in mitosis, plays essential roles diverse biological processes, especially cancer biology. In this study, NUSAP1 was found to be overexpressed GBM tissues grade-dependent manner compared with normal brain tissues. also highly expressed patients, dead and cells. addition, participate cell proliferation, apoptosis, DNA damage Ataxia telangiectasia Rad3-related (ATR) are primary sensor of damage, ATR promising target therapy. Here, we that positively regulated the expression ATR. Mechanistically, suppressed ubiquitin-dependent proteolysis The SAP (SAF-A/B, Acinus, PIAS) domain common motif many SUMO (small ubiquitin-like modifier) E3 ligases, substrate recognition ligase activity. This study further demonstrated promoted sumoylation ATR, thereby antagonized ubiquitination These results suggest stabilizes by sumoylation. Moreover, potentiated chemotherapeutic resistance temozolomide (TMZ) doxorubicin (DOX) through its domain. Overall, indicates therapeutic GBM.
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