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Journal of Virology, July 2000, p. 6031-6038, Vol. 74, No. 13
0022-538X/00/$04.00+0

Proteasome-Mediated Degradation of the Papillomavirus E2-TA Protein Is Regulated by Phosphorylation and Can Modulate Viral Genome Copy Number

Kerri J. Penrose and Alison A. McBride*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Received 2 February 2000/Accepted 7 April 2000

The bovine papillomavirus E2 proteins regulate viral transcription, replication, and episomal genome maintenance. We have previously mapped the major phosphorylation sites of the E2 proteins to serine residues 298 and 301 and shown that mutation of serine residue 301 to alanine leads to a dramatic (10- to 20-fold) increase in viral DNA copy number. In this study we analyzed how phosphorylation regulates E2 protein function. S301 is located in a PEST sequence; these sequences are often found in proteins with a short half-life and can be regulated by phosphorylation. We show here that the E2 protein is ubiquitinated and degraded by the proteasome. Mutation of serine 301 to alanine increases the half-life of E2 from approximately 50 min to 160 min. Furthermore, the A301 E2 protein shows greatly reduced ubiquitination and degradation by the proteasome. These results suggest that the E2 protein level is regulated by phosphorylation, which in turn determines viral episomal copy number.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr., MSC 0455, Bethesda, MD 20892-0455. Phone: (301) 496-1370. Fax: (301) 480-1497. E-mail: alison_mcbride{at}nih.gov.

Journal of Virology, July 2000, p. 6031-6038, Vol. 74, No. 13
0022-538X/00/$04.00+0


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