HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McShan, G. D. Articles by Wilson, V. G. Search for Related Content PubMed PubMed Citation Articles by McShan, G. D. Articles by Wilson, V. G. Agricola Articles by McShan, G. D. Articles by Wilson, V. G.

Contribution of bovine papillomavirus type 1 E1 protein residue 48 to replication function

Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA¹

Author for correspondence: Van Wilson. Fax +1 409 845 3479. e-mail v-wilson{at}tamu.edu

The E1 protein of bovine papillomavirus type 1 (BPV-1) is the origin recognition protein and is essential for the initiation of viral DNA replication. We reported previously that there is a conserved motif between residues 25 and 60 of all papillomavirus E1 proteins that resembles a casein kinase II (CKII) phosphorylation site. The corresponding serine in BPV-1, serine-48, is an efficient substrate for CKII in vitro. To examine the functional role of this potential phosphorylation site, three amino acid substitutions were constructed at serine-48. Conversion of serine-48 to a glycine (S48G) resulted in a BPV-1 genome that was unable to replicate and had reduced transformation capacity. The S48G E1 protein also failed to support replication of a BPV-1 origin-containing plasmid when expressed from a heterologous vector rather than the viral genome, indicating a direct replication defect. In contrast, conversion of serine-48 to acidic residues (S48D or S48E), which mimic the charge and structure of phosphoserine, maintained the wild-type replication phenotype. These mutational results are consistent with a replication requirement for a negative charge at serine-48, presumably supplied by in vivo phosphorylation. The mechanistic basis for the negative charge requirement was examined by testing several activities of the S48G mutant E1 protein in vivo using yeast one- and two-hybrid systems. No gross defect was observed for stability, origin binding or interaction with E2 or for E1–E1 interaction, although subtle defects in these activities would not likely be detected. Overall, the results suggest that important phosphoregulatory control of E1 replication function is mediated through the N-terminal region of this protein.

This article has been cited by other articles:

				X.-L. Bian, G. Rosas-Acosta, Y.-C. Wu, and V. G. Wilson Nuclear Import of Bovine Papillomavirus Type 1 E1 Protein Is Mediated by Multiple Alpha Importins and Is Negatively Regulated by Phosphorylation near a Nuclear Localization Signal J. Virol., March 15, 2007; 81(6): 2899 - 2908. [Abstract] [Full Text] [PDF]

				C.-Y. Hsu, F. Mechali, and C. Bonne-Andrea Nucleocytoplasmic Shuttling of Bovine Papillomavirus E1 Helicase Downregulates Viral DNA Replication in S Phase J. Virol., January 1, 2007; 81(1): 384 - 394. [Abstract] [Full Text] [PDF]

				W. Deng, B. Y. Lin, G. Jin, C. G. Wheeler, T. Ma, J. W. Harper, T. R. Broker, and L. T. Chow Cyclin/CDK Regulates the Nucleocytoplasmic Localization of the Human Papillomavirus E1 DNA Helicase J. Virol., December 15, 2004; 78(24): 13954 - 13965. [Abstract] [Full Text] [PDF]

				D. J. Davido, W. F. von Zagorski, G. G. Maul, and P. A. Schaffer The Differential Requirement for Cyclin-Dependent Kinase Activities Distinguishes Two Functions of Herpes Simplex Virus Type 1 ICP0 J. Virol., December 1, 2003; 77(23): 12603 - 12616. [Abstract] [Full Text] [PDF]

				F. MEGGIO and L. A. PINNA One-thousand-and-one substrates of protein kinase CK2? FASEB J, March 1, 2003; 17(3): 349 - 368. [Abstract] [Full Text] [PDF]

				M. West, D. Flanery, K. Woytek, D. Rangasamy, and V. G. Wilson Functional Mapping of the DNA Binding Domain of Bovine Papillomavirus E1 Protein J. Virol., December 15, 2001; 75(24): 11948 - 11960. [Abstract] [Full Text] [PDF]

				K. J. Woytek, D. Rangasamy, C. Bazaldua-Hernandez, M. West, and V. G. Wilson Effects of mutations within two hydrophilic regions of the bovine papillomavirus type 1 E1 DNA-binding domain on E1-E2 interaction J. Gen. Virol., October 1, 2001; 82(10): 2341 - 2351. [Abstract] [Full Text] [PDF]

				D. Rangasamy and V. G. Wilson Bovine Papillomavirus E1 Protein Is Sumoylated by the Host Cell Ubc9 Protein J. Biol. Chem., September 22, 2000; 275(39): 30487 - 30495. [Abstract] [Full Text] [PDF]