Intracellular forms of human NOTCH1 interact at distinctly different levels with RBP-Jkappa in human B and T cells

Callahan, Jennifer; Aster, Jon C.; Sklar, Jeffrey; Kieff, Elliott; Robertson, ES

doi:10.1038/sj.leu.2401630

Cited by 10 publications

(10 citation statements)

References 44 publications

(82 reference statements)

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“…14 However, studies in fibroblasts and EBV-transformed B cell lines have suggested that Notch signaling in B-lineage cells may be CBF-1 independent. 32,33 Pui and colleagues 21 reported that Notch-1 was not detected in normal murine BM B-lineage cells encompassing Hardy fractions A-F when analyzed by RT-PCR. In contrast, we have detected Notch-1 protein in murine CD19 + cells from BM and spleen ( Figure 5) using a rabbit antihuman Notch-1 antibody 26 that is known to cross-react with murine Notch-1.…”

Section: Figurementioning

confidence: 99%

Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells

et al. 2000

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Section: Figurementioning

confidence: 99%

Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells

et al. 2000

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“…EBNA2 stimulates the Cp and LMP1 promoters through a cellular DNA binding protein called CSL (CBF1 or RBP-Jk) (20,22,35,77). CSL can also interact with cellular coactivators, like intracellular Notch, and corepressors, like CIR, that may regulate EBV latency transcripts in the absence of EBNA2 (11,23,24,77).Epigenetic events, like DNA methylation and histone modifications, constitute another level of regulatory mechanisms for EBNA2 and LMP1 expression (3,15,16,34,39,40,51,68,70). DNA methylation of proximal promoter elements correlates with the transcription repression of EBNA2 and LMP1 transcription in type I latency (3,16,58,66).…”

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confidence: 99%

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Dynamic Chromatin Boundaries Delineate a Latency Control Region of Epstein-Barr Virus

Chau

Lieberman

2004

J Virol

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. We have used the chromatin immunoprecipitation assay to examine the chromatin architecture of the LCR in different types of EBV latency programs. We have found that histone H3 K4 methylation (H3mK4) was enriched throughout a large domain that extended from internal repeat 1 (IR1) to the terminal repeat in type III latency where EBNA2 and LMP1 genes are expressed. In type I latency where EBNA2 and LMP1 genes are transcriptionally silent, the H3mK4 domain contracts and does not enter the EBNA2 or LMP1 promoters. In contrast, histone H3 K9 methylation (H3mK9), associated with silent heterochromatin, was enriched in the EBNA2 EBNA2 and LMP1 are essential for EBV-induced cellular proliferation and immortalization of primary B lymphocytes (9, 25). However, their expression can be down-regulated during latency. At least four different gene expression patterns have been characterized for various forms of EBV latency found in different tumors or host cell types (5, 6, 53). For example, EBV immortalized lymphoblastoid cell lines (LCLs) express the full panoply of viral oncogenes in a transcription program referred to as type III latency (54). In contrast, viral latency in healthy donors or in most BL-derived cell lines expresses a more restricted transcription program referred to as type I, where EBNA2 and LMP1 transcription are repressed. EBNA2 is a transcriptional regulatory protein that binds to the LMP1 and EBNA2 promoters and enforces the type III latency program (1,17,20,22,71,78). The regulation of EBNA2 expression is, therefore, critical in determining the latency program and the proliferative capacity of EBV-infected cells.The transcriptional control of EBNA2 is complex (22,41,42,69,70,75,76). During the establishment of EBV latency, EBNA2 transcription initiates at a promoter in internal repeat 1 (IR1) referred to as Wp. Once EBNA2 protein levels reach a threshold, the protein activates a second promoter upstream of Wp, referred to as Cp. EBNA2 stimulates the Cp and LMP1 promoters through a cellular DNA binding protein called CSL (CBF1 or RBP-Jk) (20,22,35,77). CSL can also interact with cellular coactivators, like intracellular Notch, and corepressors, like CIR, that may regulate EBV latency transcripts in the absence of EBNA2 (11,23,24,77).Epigenetic events, like DNA methylation and histone modifications, constitute another level of regulatory mechanisms for EBNA2 and LMP1 expression (3,15,16,34,39,40,51,68,70). DNA methylation of proximal promoter elements correlates with the transcription repression of EBNA2 and LMP1 transcription in type I latency (3,16,58,66). Inhibitors of DNA methylation relieve this repression and induce a switch from type I to type III latency patterns of EBV gene expression (3,26). Histone modifications are also known to be important for EBNA2 regulation since transcription activation correlates with promoter-specific histone hyperacetylation and histone acetyltransferase association (2, 72). Moreover, the CSL corepressors CIR and EBNA3A/C are known to associate with

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“…EBNA2 has also been shown to induce cellular genes, which include the proto-oncogene c-myc as well as CD21, Hes-1, EBI 1 and 2, and Runx3, but the spectrum of cellular genes directly activated by EBNA2 has not yet been fully elucidated (4,5,9,31,44,48,49). This problem is further complicated by the fact that many cellular genes induced during EBV infection may be the result of cooperative activities between one or more latent proteins (18,38,46,59).…”

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EBNA2 Amino Acids 3 to 30 Are Required for Induction of LMP-1 and Immortalization Maintenance

Gordadze

Onunwor

Peng

et al. 2004

J Virol

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Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2), a direct transcriptional activator of viral and cellular genes, is required for EBV-induced B-cell transformation. The functional role of conserved regions within the amino terminus of the protein preceding the poly-proline region has yet to be fully characterized. Thus, we tested whether the EBNA2 amino-terminal 30 amino acid residues, containing evolutionarily conserved region 1, are required for stimulating viral and cellular gene expression necessary for B-cell transformation in a viral transcomplementation assay. We found that these residues are required for its ability to induce LMP-1 expression in lymphoblastoid cell lines (LCLs), to stimulate LMP-1 promoter reporter plasmids in transientcotransfection assays, and to rescue LCL growth following inactivation of endogenous wild-type EBNA2 protein. Deletion of amino acid residues 3 to 30 also impaired its ability to self-associate in coimmunoprecipitation assays. These data indicate that EBNA2 residues 3 to 30 comprise an essential domain required for induction of LMP-1 expression and, consequently, for maintenance of the immortalized phenotype of LCLs. The ability to self-associate into dimers or multimers conferred by this domain may be an important mechanism for these effects.

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Intracellular forms of human NOTCH1 interact at distinctly different levels with RBP-Jkappa in human B and T cells

Cited by 10 publications

References 44 publications

Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells

Notch-1 and Notch-2 exhibit unique patterns of expression in human B-lineage cells

Dynamic Chromatin Boundaries Delineate a Latency Control Region of Epstein-Barr Virus

EBNA2 Amino Acids 3 to 30 Are Required for Induction of LMP-1 and Immortalization Maintenance

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