检索结果-南通市图书馆

Protein stability regulators screeningassay (Pro-SRSA)： protein degradation meets theCRISPR-Cas9 library

Chinese Journal of Cancer 2016年第8期35卷 385-387页

作者： yuanzhong wu Tiebang Kang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhou 510060GuangdongPR.China

The regulation of protein stability is a fundamental issue for biophysical processes,but there has not previously been a convenient and unbiased method of identifying regulators of protein ***,as reported in the article entitled "A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25 A," recently published in Cell Discovery,our team developed a protein stability regulators screening assay(Pro-SRSA) by combining the whole-genome clustered regularly interspaced short palindromic repeats Cas9(CRISPR-Cas9) library with a dual-fluorescence-based protein stability reporter and high-throughput sequencing to screen for regulators of protein *** on our findings,we are confident that this efficient and unbiased screening method at the genome scale will be used by researchers worldwide to identify regulators of protein stability.

关键词： CRISPR-Cas9 screening, Protein stability, Cdc25A, Ubiquitination, Acetylation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Systematic screening for potential therapeutic targets in osteosarcoma through a kinome-wide CRISPR-Cas9 library

引用

Cancer Biology & Medicine 2020年第3期17卷 782-794页

作者： yuanzhong wu Liwen Zhou Zifeng Wang Xin Wang Ruhua Zhang Lisi Zheng Tiebang Kang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China

Objective:Osteosarcoma is the most common primary malignant bone ***,the survival of patients with osteosarcoma has remained unchanged during the past 30 years,owing to a lack of efficient therapeutic ***:We constructed a kinome-targeting CRISPR-Cas9 library containing 507 kinases and 100 nontargeting controls and screened the potential kinase targets in *** CRISPR screening sequencing data were analyzed with the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout(MAGeCK)Python *** functional data were applied in the 143B cell line through lenti-CRISPR-mediated gene *** clinical significance of kinases in the survival of patients with osteosarcoma was analyzed in the R2:Genomics Analysis and Visualization ***:We identified 53 potential kinase targets in *** these targets,we analyzed 3 kinases,TRRAP,PKMYT1,and TP53RK,to validate their oncogenic functions in ***1 and TP53RK showed higher expression in osteosarcoma than in normal bone tissue,whereas TRRAP showed no significant *** expression of all 3 kinases was associated with relatively poor prognosis in patients with ***:Our results not only offer potential therapeutic kinase targets in osteosarcoma but also provide a paradigm for functional genetic screening by using a CRISPR-Cas9 library,including target design,library construction,screening workflow,data analysis,and functional *** method may also be useful in potentially accelerating drug discovery for other cancer types.

关键词： Osteosarcoma kinase CRISPR-Cas9 library TRRAP PKMYT1 TP53RK

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C^(Cdh1)

引用

Chinese Journal of Cancer 2012年第9期31卷 440-448页

作者： Fenju Lai Kaishun Hu yuanzhong wu Jianjun Tang Yi Sang Jingying Cao Tiebang Kang State Key Laboratory of Oncology in South China Department of Experimental Research Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China

A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up-and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/C Cdh1 that plays a key role during mitotic exit.

关键词：有丝分裂过程核酸酶基板蛋白质含量人力 DNA链 ICL 泛素化

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites

引用

Signal Transduction and Targeted Therapy 2020年第1期5卷 1516-1527页

作者： Liwen Zhou Lisi Zheng Kaishun Hu Xin Wang Ruhua Zhang Yezi Zou Li Zhong Shang Wang yuanzhong wu Tiebang Kang Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research CenterSun Yat-sen Memorial HospitalSun Yat‐sen UniversityGuangzhouChina

Human single-stranded DNA-binding protein 1(hSSB1)is required for the efficient recruitment of the MRN complex to DNA doublestrand breaks and is essential for the maintenance of genome ***,the mechanism by which hSSB1 recruits NBS1 remains ***,we determined that hSSB1 undergoes SUMOylation at both K79 and K94 under normal conditions and that this modification is dramatically enhanced in response to DNA *** of hSSB1,which is specifically fine-tuned by PIAS2α,and SENP2,not only stabilizes the protein but also enhances the recruitment of NBS1 to DNA damage *** with defective hSSB1 SUMOylation are sensitive to ionizing radiation,and global inhibition of SUMOylation by either knocking out UBC9 or adding SUMOylation inhibitors significantly enhances the sensitivity of cancer cells to *** findings reveal that SUMOylation,as a novel posttranslational modification of hSSB1,is critical for the functions of this protein,indicating that the use of SUMOylation inhibitors(e.g.,2-D08 and ML-792)may be a new strategy that would benefit cancer patients being treated with chemo-or radiotherapy.

关键词： SSB1 damage NBS1

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

RMI2 plays crucial roles in growth and metastasis of lung cancer

引用

Signal Transduction and Targeted Therapy 2020年第1期5卷 907-909页

作者： Weixiang Zhan Yina Liu Ying Gao Run Gong Wen Wang Ruhua Zhang yuanzhong wu Tiebang Kang Denghui Wei State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center510060 GuangzhouChina The Sixth Affiliated Hospital Sun Yat-sen University510000 GuangzhouChina Department of Abdominal Oncology The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University519000 ZhuhaiGuangdongChina

Dear Editor,Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world,but its therapeutic targets are still being *** instability as a key hallmark of cancer not only contributes to cancer initiation and progression,1 but also creates vulnerabilities that are relatively specific to cancer cells,which may be potential therapeutic targets for cancer *** DNA Double-Strand Breaks(DSBs)repair,BTR(BLM-Topo IIIα-RMI1/RMI2)complex promotes the dissolution of double Holliday junctions to form non-crossover products and is often considered as a tumor suppressor.2 However,the function of each individual component of this BTR complex in cancer remains largely unknown.

关键词： cancer metastasis Lung

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer

引用

Cancer Communications 2021年第2期41卷 121-139页

作者： Ailin Chen Shijun Wen Fang Liu Zijian Zhang Meiling Liu yuanzhong wu Bin He Min Yan Tiebang Kang Eric W-F Lam Zifeng Wang Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China Institute of Cancer Stem Cell Dalian Medical UniversityDalianLiaoning 116044P.R.China Department of Surgery and Cancer Imperial College LondonW120NNLondonUK

Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse *** selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of ***,identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic ***:Here,we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with ***,we performed competitive growth assays,colony formation assays,cell viability assays,apoptosis assays,and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin(GSG2)depletion or inhibition with *** mechanistic studies,immunofluorescence was used to detect the state of microtubules and the localization of Aurora-B and mitotic centromere-associated kinesin(MCAK).Results:Among the hits,we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of *** studies showed that co-treatment with Aurora-A and Haspin inhibitors abolished the recruitment of Aurora-B and mitotic centromere-associated kinesin(MCAK)to centromeres which were associated with excessive microtubule depolymerization,kinetochore-microtubule(KT-MT)attachment failure,and severe mitotic *** further showed that the combination of MLN8237 and the Haspin inhibitor CHR-6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor ***:These findings establish Haspin as a synthetic lethal targe

关键词： alisertib Aurora-A breast cancer CHR-6494 CRISPR/Cas9 screening haspin kinetochoremicrotubule mitotic centromere-associated kinesin synthetic lethal xenograft

来源：

维普期刊数据库评论