Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin.

Seo, Yeon‐Soo; Müller, Friedemann; Lusky, Monika; Gibbs, E. Michael; Kim, Hae‐Yeong; Phillips, Barbara B.; Hurwitz, Jerard

doi:10.1073/pnas.90.7.2865

Cited by 154 publications

(163 citation statements)

References 21 publications

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“…Purified E1 protein can initiate in vitro viral replication without the support of the E2 protein (6). However, the interaction of E1 with E2 protein promotes specific binding and assembly of E1 protein on the viral origin to form an active initiation complex (7,8). Additional functions of E1 include recruiting cellular replication factors, such as the DNA polymerase ␣ and replication protein A (9 -11).…”

Section: Bovine Papillomavirus (Bpv)mentioning

confidence: 99%

SUMO-1 Modification of Bovine Papillomavirus E1 Protein Is Required for Intranuclear Accumulation

Rangasamy¹,

Woytek²,

Khan³

et al. 2000

Journal of Biological Chemistry

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The E1 protein is a multifunctional, origin-binding helicase that is essential for replication of papillomaviruses. Recently, bovine papillomavirus E1 was shown to be post-translationally modified by the addition of the SUMO-1 polypeptide. Here we show that the site of sumoylation maps to lysine residue 514. This lysine and the flanking sequences are well conserved in human papillomavirus (HPV) E1 proteins. Both HPV1a and HPV18 E1 proteins are substrates for sumoylation in vitro, which is consistent with this modification being a general property of E1 proteins. Mutations, which impair the sumoylation of bovine papillomavirus E1, prevent normal nuclear accumulation of E1 with a concomitant loss of replication capacity. These results suggest that sumoylation plays a role in nuclear transport and could regulate the E1 replication function by controlling access to the nuclear replication domains. Bovine papillomavirus (BPV)1 E1 protein is the major initiator protein for viral DNA replication and thus plays a critical role in the establishment of episomal viral genomes in the host cell nucleus (1). E1 and E2 proteins are the only two viral proteins required to replicate the viral genome in vivo, whereas the rest of the replication machinery is provided by the host cell (2, 3). E1 is a DNA helicase that binds to specific sequences in the viral origin and unwinds the viral DNA for initiation of replication (4, 5). Purified E1 protein can initiate in vitro viral replication without the support of the E2 protein (6). However, the interaction of E1 with E2 protein promotes specific binding and assembly of E1 protein on the viral origin to form an active initiation complex (7,8). Additional functions of E1 include recruiting cellular replication factors, such as the DNA polymerase ␣ and replication protein A (9 -11). E1 also interacts with histone H1 (12) and SW1/SNF5 (13), suggesting that E1 plays a role in chromatin remodeling at the viral origin.Recently, we demonstrated that BPV E1 protein is posttranslationally modified by a novel process known as sumoylation (14). Sumoylation involves the covalent attachment of the small ubiquitin-related proteins (SUMO-1, -2, or -3) to target substrates (15). Sumoylation is achieved by a multistep process in a manner that is analogous to ubiquitinylation (reviewed in Ref. 16). SUMO is first activated by a heterodimeric enzyme termed Aos1/Uba2, and then the activated SUMO is covalently transferred to the SUMO-specific conjugating enzyme Ubc9 via a thioester linkage (17). Ubc9 physically interacts with various substrates and transfers SUMO to one or more lysine residues in the target protein. Unlike ubiquitinylation in which the primary function is targeting proteins for degradation, the effects of sumoylation are more substrate-specific and can result in alterations in function (18 -20), stability (21), or intracellular location (22-25) of the modified protein. For BPV E1, a mutant unable to interact with Ubc9 showed altered intranuclear distribution (14). As BPV E1 is the first kno...

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Section: Bovine Papillomavirus (Bpv)mentioning

confidence: 99%

SUMO-1 Modification of Bovine Papillomavirus E1 Protein Is Required for Intranuclear Accumulation

Rangasamy¹,

Woytek²,

Khan³

et al. 2000

Journal of Biological Chemistry

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“…Its role during the process of initiating DNA replication is thus unclear. By establishing a molecular association with E1 (Mohr et al, 1990;Blitz & Laimins, 1991;Lusky & Fontane, 1991), E2 has been shown to improve E1 binding to the ori (Seo et al, 1993b;Lusky et al, 1993). In addition, as suggested by recent in vitro replication experiments (Li & Botchan, 1993, acidic transcription factors could increase the efficiency of DNA replication, if appropriate binding sites are replacing the E2 responsive elements that normally are located adjacent to the ori.…”

confidence: 99%

Bovine papillomavirus type 1 E1 ATPase activity does not depend on binding to DNA nor to viral E2 protein

Santucci

Bonne-Andréa²,

Clertant³

1995

Journal of General Virology

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Replication of bovine papillomavirus type 1 (BPV-I) DNA has been shown to require two viral proteins known to interact in a molecular complex: E2, a transcription activator, and El, another nuclear phosphoprotein, which binds to the replication origin and for which helicase/ATPase activities have previously been reported. Here we characterize the BPV-1 E1 ATPase activity. In contrast to Seo et al. (Proceedings of the National Academy of Sciences, USA, 90, 702-706, 1993), we were able to detect this activity in the absence of nucleic acid in partially purified preparations of either E1 protein or of El-E2 protein complex. Measurements of specific activity and kinetic parameters gave similar values for preparations of various kinds. ATPase activity was quantitatively retained by immunoprecipitates obtained by using anti-E1 or, in the case of El-E2 complex, anti-E2 antibodies. Significantly, preparations of bacterially expressed glutathione S-transferase-E1 fusion protein exhibited levels of DNA-independent ATPase activity comparable to those of baculovirusexpressed El. The presence of nucleic acids of various types, including stoichiometric amounts of a BPV-1 ori DNA fragment containing E1 and E2 binding sites, did not grossly affect E1 ATPase activity, the most notable effect being a 2-fold stimulation by unspecific ssDNA. Altogether, our results indicate that BPV-1 E1 possesses an intrinsic ATPase activity which does not depend on the presence of nucleic acid; moreover, they render unlikely any modulation of E1 ATPase activity due to binding either E2 protein or target DNA sequences, or as a result of protein phosphorylation.

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“…Furthermore, the efficiency of BPV 1 DNA replication has been shown to correlate with the affinity of E2 binding to its cognate sequences in the origin (22). The BPV1 E2 directly interacts with El (25)(26)(27), and this interaction leads to enhancement of El binding to its site within the core origin (25,(28)(29)(30). Hence, part of the role of E2 in BPV1 DNA replication relies on its capacity to tether El to the origin.…”

Section: Introductionmentioning

confidence: 99%

Control of HPV 18 DNA replication by cellular and viral transcription factors

et al. 1995

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Papillomavirus replication in vivo requires the interaction of the virally encoded proteins El and E2 with the origin of replication which is localised in the regulatory region (long control region or LCR) of the viral genome. In genital human papillomaviruses (HPVs), the origin overlaps promoter elements of early transcription. In this study, we analysed the replication of HPV18 DNA using the complete LCR containing mutations in transcription regulatory elements. We found that each of the three E2 binding sites proximal to the AT-rich sequence of the origin contributes to the replication rate of DNA, although not identically. In addition, two sequences important for early transcription, an Spi binding site and the TATA box, were also found to play a role in replication. In contrast, two AP1 binding sites required for the enhancer-mediated activation of early transcription did not affect the replication, while other upstream sequences in the LCR did contribute to the replication efficiency. Our results indicate that besides a core origin of replication containing an AT-rich sequence and three E2 binding sites, auxiliary elements affect HPVl 8 DNA replication in the context of the full length LCR, some of which are important for transcription.

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Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin.

Cited by 154 publications

References 21 publications

SUMO-1 Modification of Bovine Papillomavirus E1 Protein Is Required for Intranuclear Accumulation

SUMO-1 Modification of Bovine Papillomavirus E1 Protein Is Required for Intranuclear Accumulation

Bovine papillomavirus type 1 E1 ATPase activity does not depend on binding to DNA nor to viral E2 protein

Control of HPV 18 DNA replication by cellular and viral transcription factors

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