The Mdm2 Ubiquitin Ligase Enhances HPV E2 Transcriptional Activation

N GAMMOH, D GARDIOL, P MASSIMI AND L BANKS

JOURNAL OF VIROLOGY

ASM

Lugar: EEUU; Año: 2009 vol. 82 p. 1535 - 1543

0022-538X

The regulation of human papillomavirus (HPV) gene expression by the E2 protein is a critical feature of the viral life cycle. Previous studies have shown an important role in transcription for the ubiquitinproteasome pathway, but its role in HPV gene expression has not been addressed. We now show that HPV E2 requires an active proteasome for its optimal transcriptional activator function. This involves an interaction with the Mdm2 ubiquitin ligase, which together with E2 acts synergistically to activate the HPV type 16 promoter. We also show that HPV E2 recruits Mdm2 onto HPV promoter sequences, providing an explanation for this cooperative activity.