Research Papers:

LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis

Jana Cesnekova _, Jana Spacilova, Hana Hansikova, Josef Houstek, Jiri Zeman and Lukas Stiburek

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Oncotarget. 2016; 7:47687-47698. https://doi.org/10.18632/oncotarget.9959

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Jana Cesnekova1, Jana Spacilova1, Hana Hansikova1, Josef Houstek2, Jiri Zeman1, Lukas Stiburek1

1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic

2Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Correspondence to:

Lukas Stiburek, email: [email protected]

Keywords: p53, LACE1, mitochondria, apoptosis, translocation

Received: August 17, 2015     Accepted: May 28, 2016     Published: June 13, 2016


p53 is a major cellular tumor suppressor that in addition to its nuclear, transcription-dependent activity is also known to function extranuclearly. Cellular stressors such as reactive oxygen species can promote translocation of p53 into mitochondria where it acts to protect mitochondrial genome or trigger cell death via transcription-independent manner. Here we report that the mammalian homologue of yeast mitochondrial Afg1 ATPase (LACE1) promotes translocation of p53 into mitochondria. We further show that LACE1 exhibits significant pro-apoptotic activity, which is dependent on p53, and that the protein is required for normal mitochondrial respiratory function. LACE1 physically interacts with p53 and is necessary for mitomycin c-induced translocation of p53 into mitochondria. Conversely, increased expression of LACE1 partitions p53 to mitochondria, causes reduction in nuclear p53 content and induces apoptosis. Thus, LACE1 mediates mitochondrial translocation of p53 and its transcription-independent apoptosis.

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