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Journal of Virology, October 2009, p. 10106-10118, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00174-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Wild-Type p53 Enhances Efficiency of Simian Virus 40 Large-T-Antigen-Induced Cellular Transformation{triangledown}

Andrea Hermannstädter, Christine Ziegler, Marion Kühl, Wolfgang Deppert,* and Genrich V. Tolstonog*

Heinrich-Pette-Institute for Experimental Virology and Immunology Martinistr. 52, D-20251 Hamburg, Germany

Received 26 January 2009/ Accepted 17 July 2009

Abortive infection of BALB/c mouse embryo fibroblasts differing in p53 gene status (p53+/+ versus p53–/–) with simian virus 40 (SV40) revealed a quantitatively and qualitatively decreased transformation efficiency in p53–/– cells compared to p53+/+ cells, suggesting a supportive effect of wild-type (wt) p53 in the SV40 transformation process. SV40 transformation efficiency also was low in immortalized p53–/– BALB/c 10-1 cells but could be restored to approximately the level in immortalized p53+/+ BALB/c 3T3 cells by reconstituting wt p53, but not mutant p53 (mutp53), expression. Stable expression of large T antigen (LT) in p53+/+ 3T3 cells resulted in full transformation, while LT expression in p53–/– 10-1 cells could not promote growth in suspension or in soft agar to a significant extent. The helper effect of wt p53 is mediated by its cooperation with LT and resides in the p53 N terminus, as an N-terminally truncated p53 ({Delta}Np53) could not rescue the p53-null phenotype. The p53 N terminus serves as a scaffold for recruiting transcriptional regulators like p300/CBP and Mdm2 into the LT-p53 complex. Consequently, LT affected global and specific gene expression in p53+/+ cells significantly more than in p53–/– cells. Our data suggest that recruitment of transcriptional regulators into the LT-p53 complex may help to modify cellular gene expression in response to the needs of cellular transformation.

* Corresponding author. Mailing address: Heinrich-Pette-Institute for Experimental Virology and Immunology Martinistr. 52, D-20251 Hamburg, Germany. Phone for Wolfgang Deppert: 494048051-261 or -260. Fax: 494048051-117. E-mail: wolfgang.deppert{at}hpi.uni-hamburg.de. Phone for Genrich V. Tolstong: 494048051-235. Fax: 494048051-117. E-mail: genrich.tolstonog{at}hpi.uni-hamburg.de

{triangledown} Published ahead of print on 22 July 2009.

Journal of Virology, October 2009, p. 10106-10118, Vol. 83, No. 19
0022-538X/09/$08.00+0     doi:10.1128/JVI.00174-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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