RBP-J (CSL) Is Essential for Activation of the K14/vGPCR Promoter of Kaposi's Sarcoma-Associated Herpesvirus by the Lytic Switch Protein RTA

Liang, Yuying; Ganem, Don

doi:10.1128/jvi.78.13.6818-6826.2004

Cited by 75 publications

(79 citation statements)

References 71 publications

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“…One explanation would be that regulation of vGPCR expression in vivo might occur outside the lytic phase and initiate a cascade of events that would lead to development of angioproliferation. Indeed, studies done by Liang and Ganem (48) indicate that the vGPCR promoter can be activated by the transcription factor RBP-J, a downstream effector of the Notch pathway. Dysregulation of vGPCR expression could then provide for initiation of angioproliferation, as shown in this study and elsewhere (23,49).…”

Section: Discussionmentioning

confidence: 99%

The Human Herpes Virus 8-Encoded Chemokine Receptor Is Required for Angioproliferation in a Murine Model of Kaposi’s Sarcoma

Jensen

Manfra²,

Grisotto³

et al. 2005

The Journal of Immunology

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Kaposi’s sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively active G protein-coupled receptor known as vGPCR that binds CXC chemokines with high affinity. In this study, we show that conditional transgenic expression of vGPCR by cells of endothelial origin triggers an angiogenic program in vivo, leading to development of an angioproliferative disease that resembles KS. This angiogenic program consists partly in the expression of the angiogenic factors placental growth factor, platelet-derived growth factor B, and inducible NO synthase by the vGPCR-expressing cells. Finally, we show that continued vGPCR expression is essential for progression of the KS-like phenotype and that down-regulation of vGPCR expression results in reduced expression of angiogenic factors and regression of the lesions. Together, these findings implicate vGPCR as a key element in KS pathogenesis and suggest that strategies to block its function may represent a novel approach for the treatment of KS.

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Section: Discussionmentioning

confidence: 99%

The Human Herpes Virus 8-Encoded Chemokine Receptor Is Required for Angioproliferation in a Murine Model of Kaposi’s Sarcoma

Jensen

Manfra²,

Grisotto³

et al. 2005

The Journal of Immunology

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“…RTA is composed of an N-terminal DNA binding domain and a C-terminal transactivation domain (44). RTA transactivates various viral promoters, either directly (60)(61)(62) or by recruitment of cofactors like CSL (39,40) or C/EBP (69,70). It is required for the switch between lytic and latent replication: ectopic expression of wild-type RTA in latently infected cells induces the lytic cycle, while expression of dominant-negative mutant RTA suppresses this switch (44,45).…”

Section: Discussionmentioning

confidence: 99%

Host and Viral Proteins in the Virion of Kaposi's Sarcoma-Associated Herpesvirus

Bechtel

Winant

Ganem

2005

J Virol

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163

185

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Infection of cultured cells with Kaposi's sarcoma associated herpesvirus (KSHV) typically establishes a latent infection, in which only a few viral genes are expressed. Recently, it has been reported that a subset of lytic genes are transiently expressed very early after viral entry but that this burst of abortive lytic gene expression is terminated with the supervention of latency (H. H. Krishnan, P. P. Naranatt, M. S. Smith, L. Zeng, C. Bloomer, and B. Chandran, J. Virol. 78:3601-3620, 2004). To identify molecules imported into cells by KSHV that might influence this gene expression program, we have examined the protein composition of the KSHV particle. Immunoblotting of virus particles demonstrated that RTA, the lytic switch protein, and RAP, a viral protein that is a transcriptional and cell cycle modulator, were both incorporated into virus particles. In a second approach, polypeptides isolated from purified virions were identified by mass-spectrometric analysis of their constituent tryptic peptides. With this approach we were able to identify 18 major virion proteins, including structural, regulatory, and signaling proteins of both viral and cellular origin.

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“…Cbf1 recognizes variants of an RTGGGAA sequence motif, 86 but alternative, functional Cbf1-binding sites, such as YTGGGAA, also exist. [87][88][89][90] The interaction with N IC converts Cbf1 from a transcriptional repressor to an activator by promoting its dissociation from a complex of corepressors with concomitant recruitment of coactivators.…”

Section: Notch and Mouse Mammary Glandsmentioning

confidence: 99%

Notch, Myc and Breast Cancer

Efstratiadis

Szabolcs²,

Klinakis³

2007

Cell Cycle

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RBP-J (CSL) Is Essential for Activation of the K14/vGPCR Promoter of Kaposi's Sarcoma-Associated Herpesvirus by the Lytic Switch Protein RTA

Cited by 75 publications

References 71 publications

The Human Herpes Virus 8-Encoded Chemokine Receptor Is Required for Angioproliferation in a Murine Model of Kaposi’s Sarcoma

The Human Herpes Virus 8-Encoded Chemokine Receptor Is Required for Angioproliferation in a Murine Model of Kaposi’s Sarcoma

Host and Viral Proteins in the Virion of Kaposi's Sarcoma-Associated Herpesvirus

Notch, Myc and Breast Cancer

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