Induction and bypass of p53 during productive infection by polyomavirus.
Lytic infection by polyomavirus leads to elevated levels of p53 and induction of p53 target genes p21Cip1/WAF1 (p21) and BAX. This is seen both in polyomavirus-infected primary mouse cell cultures and in kidney tissue of infected mice. Stabilization of p53 and induction of a p53 response are accompanied by phosphorylation of p53 on serine 18, mimicking a DNA damage response. Stabilization of p53 does not depend on p19Arf interaction with mdm2. Cells infected by a mutant virus defective in binding pRb and in inducing G(1)-to-S progression show a greatly diminished p53 response. However, cells infected by wild-type virus and blocked from entering S phase by addition of mimosine still show a p53 response. These results suggest a role of E2F target genes in inducing a p53 response. Polyomavirus large T antigen coprecipitates with p53 phosphorylated on serine 18 and also with p21Cip1/WAF1. Implications of these and other findings on possible mechanisms of induction and override of p53 functions during productive infection by polyomavirus are discussed.
Dey
Dilip
D
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dahl
Jean
J
Cho
Sayeon
S
Benjamin
Thomas L
TL
D000818:Animals; D000831:Animals, Newborn; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism; D007668:Kidney / Q000821:virology; D051379:Mice; D010766:Phosphorylation; D011120:Polyomavirus / Q000472:pathogenicity*; D027601:Polyomavirus Infections / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000821:virology*; D014774:Virulence
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53