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.
Kim
Jung-Woong
JW
Department of Life Science, College of Natural Sciences, Chung-Ang University, 221 Heuksuk Dong, Dongjak Ku, Seoul 156-756, Republic of Korea.
Kim
Won-Ho
WH
Jeong
Mi-Hee
MH
Jang
Sang-Min
SM
Song
Ki-Hyun
KH
Park
Sang-Ick
SI
Song
Peter I
PI
Kang
Kyung-Hwa
KH
Choi
Kyung-Hee
KH
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