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Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Cole A,Wang Z,Coyaud E,Voisin V,Gronda M,Jitkova Y,Mattson R,Hurren R,Babovic S,Maclean N,Restall I,Wang X,Jeyaraju DV,Sukhai MA,Prabha S,Bashir S,Ramakrishnan A,Leung E,Qia YH,Zhang N,Combes KR,Ketela T,Lin F

doi

10.1016/j.ccell.2015.05.004

subject

Has Abstract

pub_date

2015-06-08 00:00:00

pages

864-76

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00180-4

journal_volume

27

pub_type

杂志文章

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