Kaposi's Sarcoma-Associated Herpesvirus Lytic Switch Protein Stimulates DNA Binding of RBP-Jk/CSL To Activate the Notch Pathway

Carroll, Kyla Driscoll; Bu, Wei; Palmeri, Diana; Spadavecchia, Sophia; Lynch, Stephen J.; Marras, Salvatore A. E.; Tyagi, Sanjay; Lukac, David M.

doi:10.1128/jvi.00746-06

Cited by 55 publications

(182 citation statements)

References 110 publications

(127 reference statements)

Supporting

Mentioning

172

Contrasting

Order By: Relevance

“…Unlike previous models that posit constitutive RBPJ association with cognate DNA (22,46), EBNA2 has been shown to increase RBPJ occupancy ∼10-to 20-fold at the hes1, cd21, cd23, and arglu1 enhancers. In comparison, Notch and Mastermind increase RBPJ association with enhancer sites by approximately two-to 2.5-fold in S2N cells and >10-fold in DmD8 cells (47), whereas Kaposi sarcoma herpes virus (KSHV) Rta substantially increases RBPJ binding to cognate DNA in activation of KSHV replication (48). At EBNA2-responsive enhancers, EBNA2 also localizes with NCoR-deficient RBPJ and up-regulates gene transcription through RBPJ.…”

Section: Discussionmentioning

confidence: 99%

EBV nuclear antigen EBNALP dismisses transcription repressors NCoR and RBPJ from enhancers and EBNA2 increases NCoR-deficient RBPJ DNA binding

Portal

Calderwood

Sommermann

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

EBV nuclear antigen 2 (EBNA2) and EBV nuclear antigen LP (EBNALP) are critical for B-lymphocyte transformation to lymphoblastoid cell lines (LCLs). EBNA2 activates transcription through recombination signal-binding immunoglobulin κJ region (RBPJ), a transcription factor associated with NCoR repressive complexes, and EBNALP is implicated in repressor relocalization. EBNALP coactivation with EBNA2 was found to dominate over NCoR repression. EBNALP associated with NCoR and dismissed NCoR, NCoR and RBPJ, or NCoR, RBPJ, and EBNA2 from matrix-associated deacetylase (MAD) bodies. In non-EBV-infected BJAB B lymphoma cells that stably express EBNA2, EBNALP, or EBNA2 and EBNALP, EBNALP was associated with hairy and enhancer of split 1 (hes1), cd21, cd23, and arginine and glutamate-rich 1 (arglu1) enhancer or promoter DNA and was associated minimally with coding DNA. With the exception of RBPJ at the arglu1 enhancer, NCoR and RBPJ were significantly decreased at enhancer and promoter sites in EBNALP or EBNA2 and EBNALP BJAB cells. EBNA2 DNA association was unaffected by EBNALP, and EBNALP was unaffected by EBNA2. EBNA2 markedly increased RBPJ at enhancer sites without increasing NCoR. EBNALP further increased hes1 and arglu1 RNA levels with EBNA2 but did not further increase cd21 or cd23 RNA levels. EBNALP in which the 45 C-terminal residues critical for transformation and transcriptional activation were deleted associated with NCoR but was deficient in dismissing NCoR from MAD bodies and from enhancer and promoter sites. These data strongly support a model in which EBNA2 association with NCoR-deficient RBPJ enhances transcription and EBNALP dismisses NCoR and RBPJ repressive complexes from enhancers to coactivate hes1 and arglu1 but not cd21 or cd23.lymphoma | notch E BV causes posttransplantation and AIDS-related lymphomas and is a cofactor in African Burkitt lymphoma (BL), and Hodgkin disease. In vitro, EBV latency III infection converts B lymphocytes to immortal lymphoblast cell lines (LCLs) (1).EBV nuclear antigen 2 (EBNA2) and EBNALP are the first proteins expressed in latency III infection (2, 3). EBNA2 is essential for B-cell transformation (4, 5) and for up-regulation of EBV latency III and cell RNA expression through CSL/CBF1/ recombination signal-binding protein for immunoglobulin κJ region (RBPJ), a DNA sequence-specific cell transcription factor (6-8). EBNA2 up-regulated cell genes include hairy and enhancer of split 1 (hes1), myc, cd21, and cd23 (2, 9, 10). The EBNA2 acidic activation domain recruits basal and activated transcription factors (TF) including TFIIB, TFIIE, TFIIH, histone acetyl transferases p300, CBP, and PCAF, and RNA polymerase II (11-16).RBPJ is in repressive complexes containing NCoR1 and -2, SKIP, and SHARP (17-23). NCoR recruits class I and II histone deacetylases (HDAC), including HDAC3, which repress transcription and associate with matrix-associated deacetylase (MAD) bodies, subnuclear sites of repressed transcription (24, 25). NCoR overexpression represses EBNA2 up-regulation of promot...

show abstract

Section: Discussionmentioning

confidence: 99%

EBV nuclear antigen EBNALP dismisses transcription repressors NCoR and RBPJ from enhancers and EBNA2 increases NCoR-deficient RBPJ DNA binding

Portal

Calderwood

Sommermann

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…All plasmids were propagated as described previously (5). The following plasmid constructs were described previously: pV5-FLc50, pV5-50⌬STAD, pcDNA3, pGal4-tk-luc, and pcDNA3.1-HisLacZ (26); pET28b-N50, pORF57-WTGL3, p57⌬4-GL3, p57⌬5-GL3, and hsp-luc (25); pcDNA3-Rta-L144A, pMalc2X-FL50, pcDNA3.1-RBP-Jk, pGST-RBP-Jk, pcDNA3.1-Myc-HisC-NICD, and pCMX-VP16-RBP-Jk (5); pK-bZIPWT-GL3b, pMalc2ϫ-FLc50-L144A, and pV5-ORF50-L144A (6); pMalc2ϫ-50⌬STAD, pMalc2ϫ-50⌬STAD⌬LR, and pV5-50⌬STAD⌬LR (3); KSHV bacmid BAC36 (52); and Gal4/VP16 (34).…”

Section: Methodsmentioning

confidence: 99%

“…Many reports agree that Rta binds to short segments of the Mta promoter directly (5,13,25,49), and additional short target sequences for Rta have been derived from screens for DNA binding to the KSHV genome (11,53). However, Rta's affinity for a short segment of the Mta promoter has been estimated to be 2 to 3 magnitudes less than its affinity for the nut-1/PAN promoter (37).…”

mentioning

confidence: 99%

“…We have modeled this process on the promoter of the essential KSHV gene Mta. Using a short, 26-bp DNA from the Mta promoter, we have shown that stimulation of RBP-Jk DNA binding requires Rta DNA binding and formation of a ternary complex between Rta, RBP-Jk, and DNA (5). Accordingly, only Rta and not activated Notch1 reactivates the complete KSHV lytic cycle (5,7).…”

mentioning

confidence: 99%

“…However, no data exist to support a contribution of extended Rta binding to the Mta promoter. Moreover, although RBP-Jk is clearly required for Rta to transactivate the Mta promoter and reactivate the virus (5,19,20), the significance of the A/T repeat in combinatorial Rta and RBP-Jk DNA binding has not been explored.…”

mentioning

confidence: 99%

See 2 more Smart Citations