Transient Viral DNA Replication and Repression of Viral Transcription Are Supported by the C-Terminal Domain of the Bovine Papillomavirus Type 1 E1 Protein

Abstract

The bovine papillomavirus type 1 E1 protein is important for viral DNA replication and transcriptional repression. It has been proposed that the full-length E1 protein consists of a small N-terminal and a larger C-terminal domain. In this study, it is shown that an E1 polypeptide containing residues 132 to 605 (which represents the C-terminal domain) is able to support transient viral DNA replication, although at a level lower than that supported by the wild-type protein. This domain can also repress E2-mediated transactivation from the P89 promoter as well as the wild-type E1 protein can.

Transcription-modulatory activities of differentially spliced cDNAs encoding the E2 protein of human papillomavirus type 16

“…The data presented in this study on the ability of the E1C cDNA to reduce E2-mediated transrepression are consistent with previous observations showing that an E1 polypeptide spanning the C-terminal domain of bovine papillomavirus type 1 (residues 132–605) is able to repress E2-mediated transactivation of the viral p89 promoter (Ferran & McBride, 1998 ). Further studies of E1C transactivation and modulation of E2 transrepression are needed.…”

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

“…In addition, the central and C-terminal regions of E1 contain the ATPase and helicase domains, although the boundaries are not well defined (MacPherson et al , 1994 ; Mansky et al , 1997 ; Sarafi & McBride, 1995 ; Yang et al , 1993 ). Interestingly, none of these mapped activities requires E1 sequences in the N-terminal 80 amino acids, and if this region is deleted entirely the protein still has some replication function (Ferran & McBride, 1998 ). In order to address possible roles for the N-terminal region, all available papillomavirus E1 protein predicted amino acid sequences were examined for conserved sequences.…”

“…From the above reports, it is apparent that the E1 protein is multifunctional and has complex regulation mediated through both post-translational modification and protein–protein interactions. Mutational studies map most E1 functions to the central and C-terminal portions of the protein and it has been reported that deletion of the first 131 amino acids yields an E1 protein that retains replication capacity, though at a reduced level (Ferran & McBride, 1998 ). In order to evaluate possible functional contributions of the N-terminal region, we previously compared the available E1 sequences for conserved features within the first 100 amino acids (McShan & Wilson, 1997 a ).…”

Chapter 4 Replication and Partitioning of Papillomavirus Genomes

“…The N-terminal domain of E1 is only required for replication in vivo (Ferran and McBride, 1998;Sun et al, 1998) and likely plays a role in regulating intracellular localization. The E1 protein shuttles from the nucleus to the cytoplasm and the N-terminal domain contains both nuclear import and export signals that are regulated by cyclin A/E-Cdk2 (Deng et al, 2004;Hsu et al, 2007;Lentz et al, 1993;Ma et al, 1999).…”