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Article: p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion

Titlep53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion
Authors
Issue Date2014
Citation
Journal of Cell Biology, 2014, v. 204, n. 7, p. 1191-1207 How to Cite?
AbstractOncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Rasdriven invasion. However, its mechanism remains poorly understood. Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton. Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the translocation of p38 mitogen-activated protein kinase (MAPK) into mitochondria and induces phosphorylation of HtrA2/Omi. Concurrently, oncogenic Ras also induces mitochondrial fragmentation, irrespective of p53 expression, causing the release of HtrA2/Omi from mitochondria into the cytosol. Phosphorylated HtrA2/Omi therefore cleaves β-actin and decreases the amount of filamentous actin (F-actin) in the cytosol. This ultimately down-regulates p130 Crk-associated substrate (p130Cas)-mediated lamellipodia formation, countering the invasive phenotype initiated by oncogenic Ras. Our novel findings provide insights into the mechanism by which p53 prevents the malignant progression of transformed cells. © 2014 Yamauchi et al.
Persistent Identifierhttp://hdl.handle.net/10722/202216
ISSN
2015 Impact Factor: 8.717
2015 SCImago Journal Rankings: 7.923
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYamauchi, Shota-
dc.contributor.authorHou, Yanyan-
dc.contributor.authorGuo, Alvinkunyao-
dc.contributor.authorHirata, Hiroaki-
dc.contributor.authorNakajima, Wataru-
dc.contributor.authorYip, Aikia-
dc.contributor.authorYu, Chenghan-
dc.contributor.authorHarada, Ichiro-
dc.contributor.authorChiam, Keng Hwee-
dc.contributor.authorSawada, Yasuhiro-
dc.contributor.authorTanaka, Nobuyuki-
dc.contributor.authorKawauchi, Keiko-
dc.date.accessioned2014-08-22T02:57:49Z-
dc.date.available2014-08-22T02:57:49Z-
dc.date.issued2014-
dc.identifier.citationJournal of Cell Biology, 2014, v. 204, n. 7, p. 1191-1207-
dc.identifier.issn0021-9525-
dc.identifier.urihttp://hdl.handle.net/10722/202216-
dc.description.abstractOncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Rasdriven invasion. However, its mechanism remains poorly understood. Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton. Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the translocation of p38 mitogen-activated protein kinase (MAPK) into mitochondria and induces phosphorylation of HtrA2/Omi. Concurrently, oncogenic Ras also induces mitochondrial fragmentation, irrespective of p53 expression, causing the release of HtrA2/Omi from mitochondria into the cytosol. Phosphorylated HtrA2/Omi therefore cleaves β-actin and decreases the amount of filamentous actin (F-actin) in the cytosol. This ultimately down-regulates p130 Crk-associated substrate (p130Cas)-mediated lamellipodia formation, countering the invasive phenotype initiated by oncogenic Ras. Our novel findings provide insights into the mechanism by which p53 prevents the malignant progression of transformed cells. © 2014 Yamauchi et al.-
dc.languageeng-
dc.relation.ispartofJournal of Cell Biology-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlep53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1083/jcb.201309107-
dc.identifier.pmid24662565-
dc.identifier.pmcidPMC3971739-
dc.identifier.scopuseid_2-s2.0-84897553749-
dc.identifier.volume204-
dc.identifier.issue7-
dc.identifier.spage1191-
dc.identifier.epage1207-
dc.identifier.eissn1540-8140-
dc.identifier.isiWOS:000333903600011-
dc.publisher.placeRockefeller University Press. The Journal's web site is located at http://www.jcb.org-

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