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Journal of Virology, January 2000, p. 193-202, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

E1B 55-Kilodalton Oncoproteins of Adenovirus Types 5 and 12 Inactivate and Relocalize p53, but Not p51 or p73, and Cooperate with E4orf6 Proteins To Destabilize p53

Sandra Wienzek,1 Judith Roth,2 and Matthias Dobbelstein1,*

Institut für Virologie, Zentrum für Mikrobiologie und Hygiene, Philipps-Universität Marburg, 35037 Marburg,1 and Zentrum für Innere Medizin, Abteilung Gastroenterologie und Stoffwechsel, Fachbereich Medizin der Philipps-Universität Marburg, 35043 Marburg,2 Germany

Received 28 June 1999/Accepted 24 September 1999

The p53 tumor suppressor protein represents a target for viral and cellular oncoproteins, including adenovirus gene products. Recently, it was discovered that several proteins with structural and functional homologies to p53 exist in human cells. Two of them were termed p51 and p73. We have shown previously that the E1B 55-kDa protein (E1B-55 kDa) of adenovirus type 5 (Ad5) binds and inactivates p53 but not p73. Further, p53 is rapidly degraded in the presence of E1B-55 kDa and the E4orf6 protein of this virus. Here, it is demonstrated that p51 does not detectably associate with E1B-55 kDa. While p53 is relocalized to the cytoplasm by E1B-55 kDa, p51's location is unaffected. Finally, p51 retains its full transcriptional activity in the presence of E1B-55 kDa. Apparently, p51 does not represent a target of Ad5 E1B-55 kDa, suggesting that the functions of p51 are distinct from p53-like tumor suppression. E1B-55 kDa from highly oncogenic adenovirus type 12 (Ad12) was previously shown to surpass the oncogenic activity of Ad5 E1B-55 kDa in various assay systems, raising the possibility that Ad12 E1B-55 kDa might target a broader range of p53-like proteins. However, we show here that Ad12 E1B-55 kDa also inhibits p53's transcriptional activity without measurably affecting p73 or p51. Moderate inhibition of p51's transcriptional activity was observed in the presence of the E4orf6 proteins from Ad5 and Ad12. p53 and Ad12-E1B-55 kDa colocalize in the nucleus and also in cytoplasmic clusters when transiently coexpressed. Finally, E1B-55 kDa and E4orf6 of Ad12 mediate rapid degradation of p53 with an efficiency comparable to that of the Ad5 proteins in human and rodent cells. Our results suggest that E1B-55 kDa of either virus type has similar effects on p53 but does not affect p73 and p51.

* Corresponding author. Mailing address: Institut für Virologie, Zentrum für Mikrobiologie und Hygiene, Philipps-Universität Marburg, Robert Koch Str. 17, 35037 Marburg, Germany. Phone: 49 6421 28 64318. Fax: 49 6421 28 68962. E-mail: dobbelst{at}mailer.uni-marburg.de.

Journal of Virology, January 2000, p. 193-202, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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