0469444 - FGÚ 2017 RIV US eng J - Journal Article
Česneková, J. - Spáčilová, J. - Hansíková, H. - Houštěk, Josef - Zeman, J. - Stibůrek, L.
LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis.
OncoTarget. Roč. 7, č. 30 (2016), s. 47687-47698. ISSN 1949-2553. E-ISSN 1949-2553
R&D Projects: GA ČR(CZ) GA13-07223S
Institutional support: RVO:67985823
Keywords : p53 * LACE1 * mitochondria * apoptosis * translocation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.168, year: 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.
Permanent Link: http://hdl.handle.net/11104/0267244