Stimulation of c-Myc Transcriptional Activity by vIRF-3 of Kaposi Sarcoma-associated Herpesvirus

Lubyová, Barbora; Kellum, M.; Frisancho, J. Augusto; Pitha, Paula M.

doi:10.1074/jbc.m706430200

Cited by 40 publications

(40 citation statements)

References 61 publications

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“…However, the mechanisms required for the oncogenic activity of vIRF-3 are not sufficiently clear. Possible cellular targets of vIRF-3 comprise not only repression of p53 (47) but also the stimulation of c-myc-dependent transcription (31), the stabilization of hypoxia-inducible factor 1␣ (HIF-1␣) (51), and inhibition of the proapoptotic cellular IRF-5 (54). Moreover, modulation of the interferon (IFN) system is an important function of vIRF-3 as expected from sequence homology.…”

mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression

Schmidt

Wies

Neipel

2011

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV) carries four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3), is expressed in latently infected primary effusion lymphoma (PEL) cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon (IFN) response. We now show that vIRF-3 also interferes with the type II interferon system and antigen presentation to the adaptive immune system. Starting with an analysis of the transcriptome, we show that vIRF-3 inhibits expression of major histocompatibility complex class II (MHC II)

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confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression

Schmidt

Wies

Neipel

2011

J Virol

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“…1) was negative for Notch1 expression, which implies HHV-8-mediated mechanisms/pathways other than Nocth1 may also have a role in the lymphomagenesis of primary effusion lymphoma. For example, among many molecules and pathways, the transcriptional activities of MYC are increased 16 and the degradation of MYC protein is prolonged 17 by HHV-8 in primary effusion lymphoma cell lines; HHV-8 also regulates the cellular transcription factor nuclear factor-k B activation pathway, which in turn protects HHV-8-infected cells against spontaneous apoptosis, 18 and maintains the latent viral life cycle. 19,20 Epstein-Barr virus, assessed by in situ hybridization for the presence of EBER, is usually present in primary effusion lymphoma according to the current WHO definition.…”

Section: Discussionmentioning

confidence: 99%

Notch1 in primary effusion lymphoma: a clinicopathological study

Wang¹,

Fuda²,

Chen³

et al. 2010

Modern Pathology

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“…Elevated Myc expression has been shown to increase cancer cell apoptosis induced by Cdk1 inhibition (24). Myc is deregulated in PEL cells (8,35,36). To evaluate whether Cdk1 is required for PEL cell survival, we treated two PEL cell lines, BC-3 and BCBL-1, or KSHV-negative DG75 cells with a 10 M concentration of a specific Cdk1 inhibitor, purvalanol A (24,25), or an equal concentration of its vehicle, dimethyl sulfoxide (DMSO).…”

Section: Resultsmentioning

confidence: 99%

Cdk1 Inhibition Induces Mutually Inhibitory Apoptosis and Reactivation of Kaposi's Sarcoma-Associated Herpesvirus

Chen

Sun

2012

J Virol

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Primary effusion lymphoma (PEL) cells are predominantly infected by the latent form of Kaposi's sarcoma-associated herpesvirus (KSHV), with virus reactivation occurring in a small percentage of cells. Latency enables KSHV to persist in the host cell and promotes tumorigenesis through viral gene expression, thus presenting a major barrier to the elimination of KSHV and the treatment of PEL. Therefore, it is important to identify cellular genes that are essential for PEL cell survival or the maintenance of KSHV latency. Here we report that cyclin-dependent kinase 1 (Cdk1) inhibition can induce both apoptosis and KSHV reactivation in a population of PEL cells. Caspases, but not p53, are required for PEL cell apoptosis induced by Cdk1 inhibition. p38 kinase is activated by Cdk1 inhibition and mediates KSHV reactivation. Interestingly, upon Cdk1 inhibition, KSHV is reactivated predominantly in the nonapoptotic subpopulation of PEL cells. We provide evidence that this is due to mutual inhibition between apoptosis and KSHV reactivation. In addition, we found that KSHV reactivation activates protein kinase B (AKT/PKB), which promotes cell survival and facilitates KSHV reactivation. Our study thus establishes a key role for Cdk1 in PEL cell survival and the maintenance of KSHV latency and reveals a multifaceted relationship between KSHV reactivation and PEL cell apoptosis.

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Stimulation of c-Myc Transcriptional Activity by vIRF-3 of Kaposi Sarcoma-associated Herpesvirus

Cited by 40 publications

References 61 publications

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression

Notch1 in primary effusion lymphoma: a clinicopathological study

Cdk1 Inhibition Induces Mutually Inhibitory Apoptosis and Reactivation of Kaposi's Sarcoma-Associated Herpesvirus

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