A fail-safe system to prevent oncogenesis by senescence is targeted by SV40 small T antigen
- 9 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 39 (10), 2170-2186
- https://doi.org/10.1038/s41388-019-1139-1
Abstract
Whereas large T antigen (LT) of simian virus 40 (SV40) promotes oncogenesis by inactivating the tumor suppressor proteins p53 and pRb, SV40 small T antigen (ST) has been thought to be dispensable for this process. However, here we show that LT promotes both oncogenic growth and senescence in human cells expressing oncogenic Ras and that this latter effect is antagonized by ST. Inactivation of p53 by LT alone promoted the senescence-associated secretory phenotype (SASP), whereas the additional expression of ST attenuated this phenotype, allowing cells to avoid oncogene-induced senescence (OIS) and thereby promoting efficient oncogenesis. ST interacts with and inhibits the function of heterochromatin protein 1–binding protein 3 (HP1BP3), a positive regulator of global microRNA biogenesis, and it thereby triggers aberrant upregulation of B-cell translocation gene 2 (BTG2), which is essential for prevention of SASP and OIS by ST. Collectively, our results indicate that the HP1BP3-BTG2 axis constitutes a fail-safe system to prevent oncogenesis by means of OIS induction, and that this system is hijacked by ST.Funding Information
- MEXT | Japan Society for the Promotion of Science (KAKENHI (18H05215, 17H06301, and 25221303), KAKENHI (17K19606, 17H05534, and 17H06011))
- Japan Agency for Medical Research and Development (P-CREATE (19cm0106105h0004))
- MEXT | Japan Science and Technology Agency (CREST (JPMJCR15G4))
This publication has 35 references indexed in Scilit:
- TIS21/BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascadeCellular Signalling, 2017
- MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2International Journal of Molecular Sciences, 2015
- miR-27a suppresses the clonogenic growth and migration of human glioblastoma multiforme cells by targeting BTG2International Journal of Oncology, 2015
- Viral Small T Oncoproteins Transform Cells by Alleviating Hippo-Pathway-Mediated Inhibition of the YAP Proto-oncogeneCell Reports, 2014
- Simian virus 40 transformation, malignant mesothelioma and brain tumorsExpert Review of Respiratory Medicine, 2011
- Four faces of cellular senescenceThe Journal of cell biology, 2011
- Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replicationNature, 2006
- Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell TransformationMolecular and Cellular Biology, 2002
- Creation of human tumour cells with defined genetic elementsNature, 1999
- Contamination of Poliovirus Vaccines With Simian Virus 40 (1955-1963) and Subsequent Cancer RatesJAMA, 1998