التفاصيل البيبلوغرافية
| العنوان: |
ORP4L Extracts and Presents PIP2 from Plasma Membrane for PLC beta 3 Catalysis : Targeting It Eradicates Leukemia Stem Cells |
| المؤلفون: |
Zhong, Wenbin, Xu, Mengyang, Li, Chanjuan, Zhu, Biying, Cao, Xiuye, Li, Dan, Chen, Huanzhao, Hu, Chunxiu, Li, Rong, Luo, Chengwei, Pan, Guoping, Zhang, Wenqiang, Lai, Chaofeng, Wang, Tong, Du, Xin, Chen, Hong, Xu, Guowang, Olkkonen, Vesa M., Lei, Pingsheng, Xu, Jun, Yan, Daoguang |
| المساهمون: |
Medicum, Department of Anatomy, University of Helsinki |
| بيانات النشر: |
Cell Press |
| سنة النشر: |
2019 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
MOLECULAR-DYNAMICS SIMULATIONS, ACUTE MYELOID-LEUKEMIA, BINDING PROTEIN, CANCER, AMBER, ACTIVATION, TRANSPORT, HALLMARKS, OSW-1, Biomedicine, Biochemistry, cell and molecular biology |
| الوصف: |
Leukemia stem cells (LSCs) are a rare subpopulation of abnormal hematopoietic stem cells (HSCs) that propagates leukemia and are responsible for the high frequency of relapse in therapies. Detailed insights into LSCs' survival will facilitate the identification of targets for therapeutic approaches. Here, we develop an inhibitor, LYZ-81, which targets ORP4L with high affinity and specificity and selectively eradicates LCSs in vitro and in vivo. ORP4L is expressed in LSCs but not in normal HSCs and is essential for LSC bioenergetics and survival. It extracts PIP2 from the plasma membrane and presents it to PLC beta 3, enabling IP3 generation and subsequentCa(2+)-dependent bioenergetics. LYZ-81 binds ORP4L competitively with PIP2 and blocks PIP2 hydrolysis, resulting in defective Ca2+ signaling. The results provide evidence that LSCs can be eradicated through the inhibition of ORP4L by LYZ-81, which may serve as a starting point of drug development for the elimination of LSCs to eventually cure leukemia. ; Peer reviewed |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
This work was supported by grants from NSFC, China (grants 81770438 and 91439122 to D.Y. and 81473138 to J.X.), the National Key Research and Development Program of China (2017YFA0505100), the Major Research Program of Guangdong Science & Technology (grants 2017A030308002 to D.Y. and 2015B010109004 to J.X.), the Academy of Finland (grant 285223 to V.M.O.), and the Sigrid Juselius Foundation, the Magnus Ehrnrooth Foundation, and the Finnish Foundation for Cardiovascular Research (to V.M.O.).; Zhong , W , Xu , M , Li , C , Zhu , B , Cao , X , Li , D , Chen , H , Hu , C , Li , R , Luo , C , Pan , G , Zhang , W , Lai , C , Wang , T , Du , X , Chen , H , Xu , G , Olkkonen , V M , Lei , P , Xu , J & Yan , D 2019 , ' ORP4L Extracts and Presents PIP2 from Plasma Membrane for PLC beta 3 Catalysis : Targeting It Eradicates Leukemia Stem Cells ' , Cell Reports , vol. 26 , no. 8 , pp. 2166-+ . https://doi.org/10.1016/j.celrep.2019.01.082; http://hdl.handle.net/10138/299984; 7baff0ee-c0d3-4339-9505-cf8479ca8c6a; 85061369840; 000459041600017 |
| الاتاحة: |
http://hdl.handle.net/10138/299984 |
| Rights: |
cc_by_nc_nd ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: |
edsbas.975D54C3 |
| قاعدة البيانات: |
BASE |