| First Author | Yamauchi S | Year | 2014 |
| Journal | J Cell Biol | Volume | 204 |
| Issue | 7 | Pages | 1191-207 |
| PubMed ID | 24662565 | Mgi Jnum | J:215810 |
| Mgi Id | MGI:5606270 | Doi | 10.1083/jcb.201309107 |
| Citation | Yamauchi S, et al. (2014) p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion. J Cell Biol 204(7):1191-207 |
| abstractText | Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Ras-driven 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 beta-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. |
