The structural protein ODV-EC27 of
            <i>Autographa californica</i>
            nucleopolyhedrovirus is a multifunctional viral cyclin

Belyavskyi, Michail; Braunagel, Sharon C.; Summers, Max D.

doi:10.1073/pnas.95.19.11205

Cited by 68 publications

(39 citation statements)

References 53 publications

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“…The baculovirus ODV-EC27 protein is a cyclin B analogue. Like the host cyclin, ODV-EC27 associates with Cdk1 to create an active kinase, but the viral complex is not degraded and exit from mitosis is inhibited (2). Baculovirus DNA replication occurs in the absence of cellular replication and is thought to be enhanced after arrest in G 2 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Davy¹,

Jackson²,

Wang³

et al. 2002

J Virol

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Human papillomavirus type 16 (HPV16) is the most common cause of cervical carcinoma. Cervical cancer develops from low-grade lesions that support the productive stages of the virus life cycle. The 16E1 ∧ E4 protein is abundantly expressed in such lesions and can be detected in cells supporting vegetative viral genome amplification. Using an inducible mammalian expression system, we have shown that 16E1 ∧ E4 arrests HeLa cervical epithelial cells in G 2 . 16E1 ∧ E4 also caused a G 2 arrest in SiHa, Saos-2 and Saccharomyces pombe cells and, as with HeLa cells, was found in the cytoplasm. However, whereas 16E1 ∧ E4 is found on the keratin networks in HeLa and SiHa cells, in Saos-2 and S. pombe cells that lack keratins, 16E1 ∧ E4 had a punctate distribution. Mutagenesis studies revealed a proline-rich region between amino acids 17 and 45 of 16E1 ∧ E4 to be important for arrest. This region, which we have termed the "arrest domain," contains a putative nuclear localization signal, a cyclin-binding motif, and a single cyclin-dependent kinase (Cdk) phosphorylation site. A single point mutation in the putative Cdk phosphorylation site (T23A) abolished 16E1 ∧ E4-mediated G 2 arrest. Arrest did not involve proteins regulating the phosphorylation state of Cdc2 and does not appear to involve the activation of the DNA damage or incomplete replication checkpoint. G 2 arrest was also mediated by the E1 ∧ E4 protein of HPV11, a low-risk mucosal HPV type that also causes cervical lesions. The E1 ∧ E4 protein of HPV1, which is more distantly related to that of HPV16, did not cause G 2 arrest. We conclude that, like other papillomavirus proteins, 16E1 ∧ E4 affects cell cycle progression and that it targets a conserved component of the cell cycle machinery.Papillomaviruses are small DNA viruses that infect the epithelial tissue of a wide range of vertebrates, including humans (47). Infection begins in cells of the basal layer, with the productive stages of the virus life cycle being initiated as these infected cells migrate toward the epithelial surface. In this way, the virus life cycle is tightly linked to the differentiation of the epithelium, which makes human papillomaviruses (HPVs) difficult to study in the laboratory (37). More than 200 papillomavirus types have been identified (12). These share a common organization of their ϳ8-kb genomes but differ in the types of epithelium they infect and the pathologies that each virus causes (47). Infection occurs at cutaneous epithelial sites, i.e., the skin, for viruses such as HPV type 1 (HPV1) or at mucosal sites (e.g., the anogenital tract or the cervix) for viruses such as HPV11 and HPV16 (47). HPVs are additionally classified from low to high risk, with low-risk viruses such as HPV11 (and HPV1) being associated solely with benign lesions (often known as warts), whereas lesions caused by highrisk viruses such as HPV16 can progress to malignancy (47). HPV16 is the most prevalent high-risk virus and is the most common causative agent of cervical cancers (68).Although the 16E1 ∧ E4 ...

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Section: Discussionmentioning

confidence: 99%

Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Davy¹,

Jackson²,

Wang³

et al. 2002

J Virol

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“…EC27, encoded by Ac144, has amino acid similarity to cellular cyclins and had been suggested to be a multifunctional cyclin (Belyavskyi et al, 1998). EC27 can interact directly with either cellular cyclin kinase cdc2 or cdk6, and the protein complex EC27-cdk6 also binds to viral proliferating cell nuclear antigen (PCNA) (Belyavskyi et al, 1998) (data not included in Fig.…”

Section: Structure-associatedmentioning

confidence: 99%

Identification of protein-protein interactions of the occlusion-derived virus-associated proteins of Helicoverpa armigera nucleopolyhedrovirus

Peng

Deng

et al. 2009

Journal of General Virology

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“…The members of the cyclin family members have a characteristic cyclin box motif described as a 32-amino-acid pattern that is also shared by the cyclin homologs encoded by herpesvirus saimiri, human herpesvirus 8, and Autographa californica nucleopolyhedrovirus (6,17,21). The consensus phosphorylation site of activated cdc2 is S/T-P-X-K/R/H (11,18).…”

mentioning

confidence: 99%

cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 U _L 42 DNA Synthesis Processivity Factor

Advani

Weichselbaum

Roizman³

2001

J Virol

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Earlier studies have shown that cdc2 kinase is activated during herpes simplex virus 1 infection and that its activity is enhanced late in infection even though the levels of cyclin A and B are decreased below levels of detection. Furthermore, activation of cdc2 requires the presence of infected cell protein no. 22 and the U L 13 protein kinase, the same gene products required for optimal expression of a subset of late genes exemplified by U S 11, U L 38, and U L 41. The possibility that the activation of cdc2 and expression of this subset may be connected emerged from the observation that dominant negative cdc2 specifically blocked the expression of U S 11 protein in cells infected and expressing dominant negative cdc2. Here we report that in the course of searching for a putative cognate partner for cdc2 that may have replaced cyclins A and B, we noted that the DNA polymerase processivity factor encoded by the U L 42 gene contains a degenerate cyclin box and has been reported to be structurally related to proliferating cell nuclear antigen, which also binds cdk2. Consistent with this finding, we report that (i) U L 42 is able to physically interact with cdc2 at both the amino-terminal and carboxyl-terminal domains, (ii) the carboxyl-terminal domain of U L 42 can be phosphorylated by cdc2, (iii) immunoprecipitates obtained with anti U L 42 antibody contained a roscovitine-sensitive kinase activity, (iv) kinase activity associated with U L 42 could be immunodepleted by antibody to cdc2, and (v) U L 42 transfected into cells associates with a nocodazole-enhanced kinase. We conclude that U L 42 can associate with cdc2 and that the kinase activity has the characteristic traits of cdc2 kinase.In this report we show that the mitotic cyclin-dependent kinase interacts with the herpes simplex virus 1 (HSV-1) protein product of the U L 42 open reading frame. The viral protein functions as a DNA polymerase-associated processivity factor. We have identified this protein as a potential virally encoded partner for cdc2 on the basis of its cyclin-like characteristics, and in this report we show that it interacts physically with cdc2. Relevant to this report are the following.(i) The roots of this investigation rest on the observation that infected-cell protein 0 (ICP0), a promiscuous transactivator encoded by the ␣0 gene, binds to and stabilizes cyclin D3 (13, 31). In the ensuing investigation it became apparent that the stabilization of cyclin D3 was not associated with the transition from G 1 to S phase of the cell cycle. Specifically, cdk2 was inactive and members of the E2F family of proteins required for transcriptional activation of the S phase genes were either sequestered in the cytoplasm or rendered inactive (2,8,23,32). It also became apparent that while HSV stabilized cyclin D3, at least two other herpesviruses, herpessaimiri virus and human herpesvirus 8, encoded cyclin D homologs (17, 21). The obvious conclusion was that herpesviruses require D cyclins although, at least in the case of HSV, for other purposes tha...

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The structural protein ODV-EC27 of Autographa californica nucleopolyhedrovirus is a multifunctional viral cyclin

Cited by 68 publications

References 53 publications

Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Identification of protein-protein interactions of the occlusion-derived virus-associated proteins of Helicoverpa armigera nucleopolyhedrovirus

cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 U _L 42 DNA Synthesis Processivity Factor

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The structural protein ODV-EC27 of Autographa californica nucleopolyhedrovirus is a multifunctional viral cyclin

Cited by 68 publications

References 53 publications

Identification of a G 2 Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Identification of a G 2 Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Identification of protein-protein interactions of the occlusion-derived virus-associated proteins of Helicoverpa armigera nucleopolyhedrovirus

cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 U L 42 DNA Synthesis Processivity Factor

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Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

Identification of a G ₂ Arrest Domain in the E1∧E4 Protein of Human Papillomavirus Type 16

cdc2 Cyclin-Dependent Kinase Binds and Phosphorylates Herpes Simplex Virus 1 U _L 42 DNA Synthesis Processivity Factor