LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis
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...
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| Veröffentlicht in: | Oncotarget 2016-07, Vol.7 (30), p.47687-47698 |
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| creator | Cesnekova, Jana Spacilova, Jana Hansikova, Hana Houstek, Josef Zeman, Jiri Stiburek, Lukas |
| description | 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. |
| doi_str_mv | 10.18632/oncotarget.9959 |
| format | Article |
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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. 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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free E- Journals; PubMed Central Open Access |
| subjects | Adenosine Triphosphatases - metabolism Apoptosis - physiology HEK293 Cells Humans Mitochondria - metabolism Mitochondrial Proteins - metabolism Research Paper Transfection Tumor Suppressor Protein p53 - metabolism |
| title | LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis |
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