p19(ras) amplifies p73beta-induced apoptosis through mitochondrial pathway.
p73 and p53 have been known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homolog of p53 tumor suppressor gene, much less is known about the mechanism of p73-induced apoptotic cell death. In this study, we demonstrate that p19(ras) interaction with p73beta amplifies p73beta-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential (DeltaPsi(m)). Furthermore, endogenous expression of p19(ras) and p73beta is significantly increased by Taxol treatment, and Taxol-enhanced endogenous p73beta transcriptional activities are further amplified by p19(ras), which markedly increased cellular apoptosis in p53-null SAOS2 cancer cell line. These results have important implications for understanding the molecular events of p19(ras) to p73 functions in cancer cells.
Department of Life Science, College of Natural Sciences, Chung-Ang University, 221 Heuksuk Dong, Dongjak Ku, Seoul 156-756, Republic of Korea.
Jung-Woong
JW
Kim
Won-Ho
WH
Kim
Mi-Hee
MH
Jeong
Sang-Min
SM
Jang
Ki-Hyun
KH
Song
Sang-Ick
SI
Park
Peter I
PI
Song
Kyung-Hwa
KH
Kang
Kyung-Hee
KH
Choi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D021381:Protein Transport; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D016283:Proto-Oncogene Proteins p21(ras); D017239:Paclitaxel