Identification of a Cellular Protein That Interacts and Synergizes with the RTA (ORF50) Protein of Kaposi's Sarcoma-Associated Herpesvirus in Transcriptional Activation

Wang, Shizhen; Liu, Shuhong; Wu, Ming‐Hoi; Geng, Yi; Wood, Charles

doi:10.1128/jvi.75.24.11961-11973.2001

Cited by 80 publications

(82 citation statements)

References 47 publications

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“…The ORF 50/Rta transactivator interacts with many host cellular transcription regulators, such as CCAAT/enhancer-binding protein ␣ (72, 73), Sp1 (74), octamer-binding protein (Oct-1) (75), STAT3 (76), CREB-binding protein (77), SWI/SNF (78), TRAP/Mediator (78), MGC 2663 (79), and p53 (80). Hence, we set out to test the hypothesis that ORF 50/Rta can repress LANAp.…”

Section: Lana Protein Binds To An Essential Gc Box/sp1 Motif In Its Ownmentioning

confidence: 99%

Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus

Jeong

Orvis

Kim

et al. 2004

Journal of Biological Chemistry

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Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at ؊29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.

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Section: Lana Protein Binds To An Essential Gc Box/sp1 Motif In Its Ownmentioning

confidence: 99%

Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus

Jeong

Orvis

Kim

et al. 2004

Journal of Biological Chemistry

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“…However, other sites that are activated by RTA in vivo-for example, those in the MTA and RAP (K8, K-bZIP) promoters-display no homology to the PAN promoter site, raising the question of whether RTA might have other modes of DNA interaction, such as binding to cellular DNA binding factors. In fact, interaction with one host protein, the Zn-fingercontaining protein MGC2663, has been reported (Wang et al 2001), though it is not clear whether this protein targets RTA to DNA or is itself targeted to DNA by RTA.…”

mentioning

confidence: 99%

The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jκ (CSL), the target of the Notch signaling pathway

et al. 2002

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The RTA protein of the Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is responsible for the switch from latency to lytic replication, a reaction essential for viral spread and KS pathogenesis. RTA is a sequence-specific transcriptional activator, but the diversity of its target sites suggests it may act via interaction with host DNA-binding proteins as well. Here we show that KSHV RTA interacts with the RBP-J protein, the primary target of the Notch signaling pathway. This interaction targets RTA to RBP-J recognition sites on DNA and results in the replacement of RBP-J 's intrinsic repressive action with activation mediated by the C-terminal domain of RTA. Mutation of such sites in target promoters strongly impairs RTA responsiveness. Similarly, such target genes are induced poorly or not at all by RTA in fibroblasts derived from RBP-J −/− mice, a defect that can be reversed by expression of RBP-J . In vitro, RTA binds to two adjacent regions of RBP-J , one of which is identical to the central repression domain that binds the Notch effector fragment. These results indicate that KSHV has evolved a ligand-independent mechanism for constitutive activation of the Notch pathway as a part of its strategy for reactivation from latency.

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“…On the other hand, similar to ZNF268, a few other KRAB-containing zinc finger proteins are known to function as transcriptional activators. Among them are ZNF322 (21), ZNF445 (22) and K-RBP (23).…”

Section: Discussionmentioning

confidence: 99%

KRAB-containing zinc finger gene ZNF268 encodes multiple alternatively spliced isoforms that contain transcription regulatory domains

Shao

Zhu²,

Zhao³

et al. 2006

Int J Mol Med

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Abstract. The ZNF268 gene was originally isolated from an early human embryo cDNA library. Several different transcripts have been isolated for the ZNF268 gene and developmental expression studies suggest that ZNF268 plays a role in the development of human fetal liver and the differentiation of blood cells. In our effort to study the functions of ZNF268 in different organs during development and in pathogenesis, we have now identified 3 novel splicing isoforms, ZNF268e, ZNF268f and ZNF268g, in human fetal tissues and human tumor derived cell lines. The 8 alternatively spliced mRNAs discovered so for are predicted to encode 3 protein isoforms. Expression analysis showed that different mRNA isoforms have different expression profiles. In particular, ZNF268c mRNA was detected only in tumor cells, and ZNF268f appeared to be tissue-specific. By Western blot analysis, all 3 ZNF268 protein isoforms, ZNF268a, ZNF268b1 and ZNF268b2, were expressed in tumor cell lines, while only two protein products, ZNF268b1 and ZNF268b2, were detected in human fetal tissues. Subcellular localization analysis showed that ZNF268a and ZNF268b2 distributed diffusely throughout the cell, while ZNF268b1 mainly localized in the cytoplasm. Moreover, using a CAT reporter system fused to the Gal4 DNA binding domain of the ZNF268 gene, the ZNF268a and b2 activated the CAT reporter gene expression, while the KRAB domain, corresponding to the ZNF268b1 repressed the reporter gene expression. Taken together, our results showed that multiple ZNF268 splicing products encode multiple ZNF268 protein isoforms with different subcellular localization, and that the ZNF268 gene may function as a transcriptional activator in the growth and differentiation of cells in development and/or pathogenesis.

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Identification of a Cellular Protein That Interacts and Synergizes with the RTA (ORF50) Protein of Kaposi's Sarcoma-Associated Herpesvirus in Transcriptional Activation

Cited by 80 publications

References 47 publications

Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus

Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus

The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jκ (CSL), the target of the Notch signaling pathway

KRAB-containing zinc finger gene ZNF268 encodes multiple alternatively spliced isoforms that contain transcription regulatory domains

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