| Literature DB >> 26058080 |
Alicia Cole1, Zezhou Wang1, Etienne Coyaud1, Veronique Voisin2, Marcela Gronda1, Yulia Jitkova1, Rachel Mattson1, Rose Hurren1, Sonja Babovic3, Neil Maclean1, Ian Restall1, Xiaoming Wang1, Danny V Jeyaraju1, Mahadeo A Sukhai1, Swayam Prabha1, Shaheena Bashir2, Ashwin Ramakrishnan1, Elisa Leung4, Yi Hua Qia5, Nianxian Zhang6, Kevin R Combes5, Troy Ketela7, Fengshu Lin1, Walid A Houry4, Ahmed Aman8, Rima Al-Awar9, Wei Zheng10, Erno Wienholds11, Chang Jiang Xu2, John Dick11, Jean C Y Wang11, Jason Moffat7, Mark D Minden11, Connie J Eaves3, Gary D Bader2, Zhenyue Hao1, Steven M Kornblau5, Brian Raught1, Aaron D Schimmer12.
Abstract
From an shRNA screen, we identified ClpP as a member of the mitochondrial proteome whose knockdown reduced the viability of K562 leukemic cells. Expression of this mitochondrial protease that has structural similarity to the cytoplasmic proteosome is increased in leukemic cells from approximately half of all patients with AML. Genetic or chemical inhibition of ClpP killed cells from both human AML cell lines and primary samples in which the cells showed elevated ClpP expression but did not affect their normal counterparts. Importantly, Clpp knockout mice were viable with normal hematopoiesis. Mechanistically, we found that ClpP interacts with mitochondrial respiratory chain proteins and metabolic enzymes, and knockdown of ClpP in leukemic cells inhibited oxidative phosphorylation and mitochondrial metabolism.Entities:
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Year: 2015 PMID： 26058080 PMCID： PMC4461837 DOI： 10.1016/j.ccell.2015.05.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743