Walleye dermal sarcoma virus Orf B functions through receptor for activated C kinase (RACK1) and protein kinase C

Daniels, Candelaria C.; Rovnak, Joel; Quackenbush, Sandra L.

doi:10.1016/j.virol.2008.01.034

Cited by 19 publications

(15 citation statements)

References 63 publications

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“…Up to now, it has been reported that RACK1 can be hijacked by viruses to affect viral replication, such as Epstein-Barr virus (55), mumps virus (56), sarcoma virus (57), and hepatitis C virus (58). Consistent with these reports, in this study we also found that knockdown of RACK1 suppressed IBDV growth.…”

Section: Discussionsupporting

confidence: 91%

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

Lin

Zhang

et al. 2015

Journal of Biological Chemistry

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Background: IBDV VP5 protein induces apoptosis in DF-1 cells via interaction with VDAC2. Results: RACK1 inhibits IBDV-induced apoptosis, enhances viral replication, and interacts with both VDAC2 and VP5. Conclusion: RACK1 forms a complex with VDAC2 and VP5, affecting IBDV-induced apoptosis and viral replication. Significance: RACK1 inhibits apoptosis via interaction with VDAC2, indicating sequestration of RACK1 and VDAC2 by VP5 during IBDV infection.

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Section: Discussionsupporting

confidence: 91%

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

Lin

Zhang

et al. 2015

Journal of Biological Chemistry

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“…These models suggest that wounding activates the MAPK pathway and initiates uncontrolled IEG expression and cell transformation. While walleye dermal sarcoma might occur in association with natural wound sites on fish, during tumor growth, WDSV produces another protein, Orf B, which is capable of persistent signal activation without external stimuli (5,7,95). It is localized in the cytoplasm and plasma membranes (7,8,95) and constitutively activates protein kinase C alpha (PKC␣) in NIH 3T3 cells (95).…”

Section: Discussionmentioning

confidence: 99%

Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Birkenheuer

Brewster

Quackenbush

et al. 2015

J Virol

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Walleye dermal sarcoma virus (WDSV) infection is associated with the seasonal development and regression of walleye dermal sarcoma. Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. CDK8 is evolutionarily conserved and is frequently overexpressed in human cancers. It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. The IEGs drive cell proliferation, and their expression is brief and highly regulated. Here we show that constitutive expression of RV-cyclin in the HCT116 colon cancer cell line significantly increases the level of IEG expression in response to serum stimulation. Quantitative reverse transcription-PCR (RT-PCR) and nuclear run-on assays provide evidence that RV-cyclin does not alter the initiation of IEG transcription but does enhance the overall rate of transcription elongation and maintains transcription reinitiation. RVcyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. At the EGR1 gene locus, RV-cyclin increases and maintains RNA polymerase II (Pol II) occupancy after serum stimulation, in conjunction with increased and extended EGR1 gene expression. The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. Both of RV-cyclin's functional domains, i.e., the cyclin box and the activation domain, are necessary for the overall enhancement of IEG expression. RV-cyclin presents a novel and ancient mechanism of retrovirus-induced oncogenesis. IMPORTANCEThe data reported here are important to both virology and cancer biology. The novel mechanism pinpoints CDK8 in the development of walleye dermal sarcoma and sheds light on CDK8's role in many human cancers. CDK8 controls expression from highly regulated genes, including the interferon-stimulated genes. Its function is likely the target of many viral interferon-resistance mechanisms. CDK8 also controls cellular responses to metabolic stimuli, stress, and hypoxia, in addition to the serum response. The retroviral cyclin (RV-cyclin) represents a highly selected probe of CDK8 function. RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. The outcomes of this research are applicable to investigations of normal and abnormal CDK8 functions. The mechanisms defined here will contribute directly to the dermal sarcoma model in fish and clarify an important path for oncogenesis and innate resistance to viruses. T he complex retrovirus walleye dermal sarcoma virus (WDSV) is associated with the seasonal development and regression of dermal sarcoma in walleye fish (Sander vitreus) (1-7). The seasonal nature of the tumor is coupled with a...

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“…PKC activation may contribute to cell survival and proliferation. RV-cyclin and Orf B probably cooperate to cause efficient tumor formation (Daniels et al 2008, Rovnak andQuackenbush 2010).…”

Section: Retroviruses Associated With Skin Tumors In Walleyesmentioning

confidence: 99%

Retroviruses of wild and cultured fish

Lepa¹,

Siwicki²

2011

Polish Journal of Veterinary Sciences

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Retroviruses comprise a large group of enveloped RNA viruses which have been found in a wide range of vertebrate species including fish. To date a number of fish retrovirus genomes have been partially or completely sequenced. Phylogenetic analysis and genome organization indicate a high diversity of fish retroviruses as well as some unique structural features that have not been found in any other retroviruses. Piscine retroviruses comprise both exogenous and endogenous viruses; most of them are associated with proliferative diseases. Because several of these proliferative diseases have a seasonal trend, they provide an excellent model for studying tumor development and regression. The aim of this work was to review the best-described fish retroviruses.

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Walleye dermal sarcoma virus Orf B functions through receptor for activated C kinase (RACK1) and protein kinase C

Cited by 19 publications

References 63 publications

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Retroviruses of wild and cultured fish

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