Direct Interactions of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation

Carroll, Kyla Driscoll; Khadim, Farah; Spadavecchia, Sophia; Palmeri, Diana; Lukac, David M.

doi:10.1128/jvi.00265-07

Cited by 44 publications

(92 citation statements)

References 105 publications

(124 reference statements)

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“…Previous studies have shown that C/EBP␣ can contribute to Rta transactivation of KSHV promoters (43,44), and CAAT boxes are critical components for Rta to participate in productive replication at KSHV ori-Lyt elements (33,(45)(46)(47). We previously showed that the sequence of the Mta 5D element, containing 3 CANT repeats, is highly conserved in the K-bZIP promoter (6,25); we now note that the core sequences of Mta CANT repeats 2F, 2R, and 3R are conserved in KbZIP. Importantly, we showed that C/EBP␣ does not bind to those CANT sequences (6), and in the present study, we show instead that those CANT repeats contribute to high-affinity Rta binding.…”

Section: Discussionsupporting

confidence: 60%

“…Transcriptional mutants of Rta that are deficient in reactivating KSHV do not stimulate RBP-Jk DNA binding. We recently described a series of Rta mutants that are debilitated in transactivation and reactivation (3,6). Two of these Rta mutants, Rta-L144A, which cannot bind to DNA, and Rta⌬LR, which cannot form tetramers, both failed to form ternary complexes with RBP-Jk on the Mta Ϫ136/Ϫ62 WT DNA.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, each of these fragments contains at least 1 RBP-Jk element straddled by one or more palindromes or repeats. Many of the fragments contain ORFs whose promoters are known targets of Rta, such as the HindIII 2,026-bp fragment (ORF57 [5,13,25,49]) and the HindIII 3,038-bp fragment (K8 [6]) ( Table 1). The exception to these observations is the 1.5-kb SacI band, which might have hybridized to juxtaposed genomic fragments that contained RBP-Jk sites.…”

Section: Discussionmentioning

confidence: 99%

“…Rta interacts directly with a number of cellular transcription factors to activate transcription of viral genes (6,19,42,43). Among these cellular proteins, binding of Rta to RBP-Jk is essential for viral reactivation (20).…”

mentioning

confidence: 99%

“…EMSA was performed exactly as described in references 5 and 6. 5C, 5D, and 5E DNAs were prepared by annealing oligonucleotides, as previously described (5,6). Mta Ϫ136/Ϫ62 DNA was generated by PCR amplification from the plasmid pORF57-WTGL3 and purified by electroelution from agarose gels.…”

mentioning

confidence: 99%

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Kaposi's Sarcoma-Associated Herpesvirus Rta Tetramers Make High-Affinity Interactions with Repetitive DNA Elements in the Mta Promoter To Stimulate DNA Binding of RBP-Jk/CSL

Palmeri

Carroll

González‐López

et al. 2011

J Virol

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Section: Discussionsupporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Kaposi's Sarcoma-Associated Herpesvirus Rta Tetramers Make High-Affinity Interactions with Repetitive DNA Elements in the Mta Promoter To Stimulate DNA Binding of RBP-Jk/CSL

Palmeri

Carroll

González‐López

et al. 2011

J Virol

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Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

He¹,

Cheng²,

Silva³

et al. 2018

Cancer Treatment and Research

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Discovered in 1994, KSHV is a human oncogenic gammaherpesvirus [1]. KSHV is causatively associated with several malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and KSHV inflammatory cytokine syndrome (KICS), most of which are commonly found in HIV-1infected individuals [1,2,3,4]. KS is a multifocal mesenchymal neoplasm characterized by neo-angiogenesis, inflammatory infiltration, and spindle-shaped tumor cells that express mixed cellular markers, including vascular and lymphatic endothelial, mesenchymal, and hematopoietic precursor cells [5]. Early stage of KS primarily affects mucocutaneous tissues but advanced stage of KS is often involved with visceral organs [5]. KS is one of the most common malignancies in AIDS patients. While the advent of antiretroviral therapy has substantially reduced the incidence of KS in Western countries, it has stabilized or even rebound in recent years in some populations, and continues to be the most common cancer in some African regions [6]. Hence, KS remains to be one of the most important malignancies in AIDS patients causing significant morbidity and mortality.PEL is a rare and aggressive non-Hodgkin's B cell lymphoma clinically characterized by lymphomatous effusions in body cavities usually without tumor masses [7]. PEL often occurs in advanced AIDS patients with a decreased CD4 T cell count at diagnosis. Approximately, half of PEL patients have KS or are at risk for developing KS. PEL is resistant to conventional chemotherapy with a short median survival of less than 6 months [7].MCD is a polyclonal B cell lymphoproliferative disorder characterized by inflammatory symptoms, including fever, cachexia, lymphadenopathy, splenomegaly, cytopenia, and hypoalbuminemia [8]. MCD in the setting of HIV is typically associated with KSHV infection and is usually fatal without treatment. Furthermore, there is no established standard of treatment for KSHV-associated MCD [8].

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Number of and distance between response elements in Kaposi’s sarcoma-associated herpesvirus ORF57 promoter influence its activation by replication and transcription activator and its repression by interferon regulatory factor 7

Liu

Shi

et al. 2009

Arch Virol

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Kaposi’s sarcoma-associated herpesvirus ORF57 expression is highly responsive to replication and transcription activator (RTA) and interferon regulatory factor 7 (IRF-7). Three RTA response elements (RREs) have been identified in the ORF57 promoter. Here, we show evidence of another functional RRE located between nt 82003 and 82081, which can complement the loss of RTA activation resulting from RRE1 deletion. Repeats of a recombination signal-binding protein Jκ (RBP-Jκ) site enhanced RTA activation, which could not be suppressed by IRF-7. Alteration of the distance between the RBP-Jκ site and RRE2 modulated responsiveness to RTA and IRF-7. These results will help to elucidate the precise regulation of viral gene expression.

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Direct Interactions of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation

Cited by 44 publications

References 105 publications

Kaposi's Sarcoma-Associated Herpesvirus Rta Tetramers Make High-Affinity Interactions with Repetitive DNA Elements in the Mta Promoter To Stimulate DNA Binding of RBP-Jk/CSL

Kaposi's Sarcoma-Associated Herpesvirus Rta Tetramers Make High-Affinity Interactions with Repetitive DNA Elements in the Mta Promoter To Stimulate DNA Binding of RBP-Jk/CSL

Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

Number of and distance between response elements in Kaposi’s sarcoma-associated herpesvirus ORF57 promoter influence its activation by replication and transcription activator and its repression by interferon regulatory factor 7

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