Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Oncogene
T H ChangR Schlegel

Abstract

SV40 large T antigen (T) inactivates the tumor suppressor proteins p53 and pRb, and can induce cells to enter DNA replication at inappropriate times. We show here that T also compromises three cell cycle checkpoints that regulate the entry into and exit from mitosis. Human diploid fibroblasts infected with a retrovirus expressing T displayed an attenuated radiation-induced mitotic delay, were more susceptible to chemical-induced uncoupling of mitosis from the completion of DNA replication, and were more likely to exit mitosis and rereplicate their DNA when mitotic spindle assembly was inhibited. Consistent with altered mitotic checkpoint control, cells expressing T displayed elevated protein levels and/or associated activities of the mitotic regulatory proteins cyclin A, cyclin B, Cdc25C and p34(cdc2). These changes in mitotic control were evident within 5-10 population doublings after retroviral infection, indicating a direct effect of T expression. Cells acutely infected with the T-expressing retrovirus suffered numerical and structural chromosome aberrations, including increases in aneuploidy, dicentric chromosomes, chromatid exchanges and chromosome breaks and gaps. These findings indicate that T rapidly disrupts mitotic ch...Continue Reading

Citations

Jan 1, 1997·Brain Tumor Pathology·S O SuzukiT Iwaki
Jan 15, 2009·Genetica·L P G D'ArceE T Sakamoto-Hojo
Apr 16, 2004·DNA Repair·Cristina SwansonRaymond J Monnat
Oct 16, 2002·Mutation Research·Carla SantanaAlejandro García-Carrancá
Oct 22, 2003·Archives of Medical Research·Carla S Lopes, Claudio E Sunkel
Aug 5, 2000·Free Radical Biology & Medicine·R E ShackelfordR S Paules
Jun 17, 2005·The American Journal of Surgical Pathology·Neeraja KambhamTeri A Longacre
Aug 21, 2002·Journal of Virology·Dilip DeyThomas L Benjamin
Sep 29, 2005·Journal of Virology·Jean DahlThomas L Benjamin
Oct 22, 2008·Annual Review of Pathology·David R McGivern, Stanley M Lemon
Feb 23, 2012·The Journal of Clinical Investigation·Laure GineauEmmanuelle Jouanguy
May 7, 1999·Environmental Health Perspectives·R E ShackelfordR S Paules
Jan 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Marina CotsikiOle V Gjoerup
Dec 29, 2000·The Journal of Eukaryotic Microbiology·M ScanlonG J Leitch
Dec 14, 1999·The Journal of Investigative Dermatology·C C ZouboulisC E Orfanos
May 10, 2005·Cell Motility and the Cytoskeleton·Piero A BattagliaFranca Gigliani
Apr 20, 2007·Journal of Cellular Physiology·Peter PelkaPeter Whyte
Jul 26, 2011·Molecular Reproduction and Development·Marcin ChruscielAneta Andronowska
Feb 1, 2005·Virus Research·G Joan GrindlayVincent O'Brien
Oct 13, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Martyn K White, Kamel Khalili
Aug 2, 2005·Lancet·Bruce W S RobinsonRichard A Lake
Jun 29, 2005·Brain Research. Brain Research Reviews·Martyn K WhiteKamel Khalili
Jun 10, 2014·Journal of Hepatology·Eva RamboerMathieu Vinken
Apr 28, 2004·Developmental Biology·Ted Hung-Tse ChangMargaret Buckingham
Aug 17, 1999·Seminars in Cancer Biology·G A Pihan, S J Doxsey
May 26, 2017·Molecular Biology of the Cell·Hazheen K ShirnekhiJacob A Herman
Feb 19, 2002·Oncogene·Simon W-L Chan, Elizabeth H Blackburn
Apr 21, 2001·Oncogene·W R Taylor, G R Stark
Mar 21, 2008·American Journal of Physiology. Cell Physiology·Stephen H K WongKai Y Lei
Jan 23, 2020·Viruses·Lenka HorníkováJitka Forstová

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