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Published on: August 25, 2017
Retroviral oncogenes and TOR
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC-239, La Jolla, CA 92037, USA.
Abstract:
Retroviruses have recruited the catalytic subunit of PI 3-kinase and its downstream target, Akt, as oncogenes. These viruses cause tumors in animals and induce oncogenic transformation in cell culture. The oncogenicity of these viruses is specifically inhibited by rapamycin; retroviruses carrying other oncogenes are insensitive to this macrolide antibiotic. Rapamycin is an inhibitor of the TOR (target of rapamycin) kinase whose downstream targets include p70 S6 kinase and the negative regulator of translation initiation 4E-BP. Emerging evidence suggests that the TOR signals transmitted to the translational machinery are essential for oncogenic transformation by the PI 3-kinase pathway.
Insights
Certain retroviruses use PI 3-kinase and Akt as oncogenes, causing tumors. Their oncogenicity is blocked by rapamycin, an inhibitor of the target of rapamycin (TOR) kinase pathway, crucial for cell transformation.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Retroviruses can act as oncogenes by incorporating PI 3-kinase and Akt.
- These viral oncogenes induce tumors in vivo and transformation in vitro.
Purpose of the Study:
- To investigate the role of the target of rapamycin (TOR) pathway in retroviral oncogenesis.
- To determine the specificity of rapamycin's inhibitory effect on these oncogenic retroviruses.
Main Methods:
- Utilized retroviral models expressing PI 3-kinase and Akt.
- Assessed oncogenic transformation in cell culture and tumor formation in animals.
- Tested the sensitivity of these viruses to rapamycin treatment.
Main Results:
- Rapamycin specifically inhibited the oncogenicity of retroviruses utilizing PI 3-kinase/Akt.
- Retroviruses with different oncogenes were insensitive to rapamycin.
- Rapamycin targets the TOR kinase, affecting p70 S6 kinase and 4E-BP.
Conclusions:
- The PI 3-kinase/Akt pathway's oncogenic transformation is dependent on TOR signaling.
- TOR signaling to the translational machinery is essential for PI 3-kinase-driven oncogenesis.
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