Interaction with CBP/p300 enables the bovine papillomavirus type 1 E6 oncoprotein to downregulate CBP/p300-mediated transactivation by p53.
The E6 oncoprotein of bovine papillomavirus type 1 (BPV-1) can transform cells independently of p53 degradation. The precise mechanisms underlying this transformation are not yet completely understood. Here it is shown that BPV-1 E6 interacts with CBP/p300 in the same way as described for the E6 proteins of oncogenic human papillomaviruses. This interaction results in an inhibition of the transcriptional coactivator function of CBP/p300 required by p53 and probably by other transcription factors. The comparison of the CBP/p300-binding properties of BPV-1 E6 mutants previously characterized in transcription and transformation studies suggests (i) that the E6-CBP/p300 interaction may be necessary, but not sufficient, for cell transformation, and (ii) that the transcriptional activator function, inherent to the E6 protein, is not derived from forming a complex with CBP/p300.
Zimmermann
Holger
H
Laboratory for Papillomavirus Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore1.
Koh
Choon-Heng
CH
Laboratory for Papillomavirus Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore1.
Degenkolbe
Roland
R
Laboratory for Papillomavirus Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore1.
O'Connor
Mark J
MJ
Laboratory for Papillomavirus Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore1.
Müller
Andreas
A
Institut für Virologie der Universität zu Köln, Cologne, Germany2.
Steger
Gertrud
G
Institut für Virologie der Universität zu Köln, Cologne, Germany2.
Chen
Jason J
JJ
Department of Dermatology, New England Medical Center, Boston, MA, USA3.
Lui
Yun
Y
Department of Dermatology, New England Medical Center, Boston, MA, USA3.
Androphy
Elliot
E
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA4.|Department of Dermatology, New England Medical Center, Boston, MA, USA3.
Bernard
Hans-Ulrich
HU
Laboratory for Papillomavirus Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore1.
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D002417:Cattle; D002460:Cell Line; D002472:Cell Transformation, Viral; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation
D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D015534:Trans-Activators; C059269:protein E6, Bovine papillomavirus