Epstein–Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells

Maruo, Seiji; Wu, Yi; Ishikawa, Satoko; Kanda, Teru; Iwakiri, Dai; Takada, Kenzo

doi:10.1073/pnas.0604919104

Cited by 94 publications

(162 citation statements)

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“…Although EBNA3C down-regulated pRb RNA 1.5-fold, with FDR < 0.001, under nonpermissive conditions for EBNA3CHT expression, EBNA3CHT levels decreased, but pRb protein levels did not increase, suggesting that pRb turnover is increased in the absence of EBNA3C or that pRb is less well detected (14). EBNA3C also down-regulated p16 and p14 RNAs 1.4-fold with FDR <5 × 10 −4 and p16 expression likely caused pRb hypophosphorylation.…”

Section: Ebna3c-regulated Genes Overlap With Ebna2-and Ebna3a-regulatedmentioning

confidence: 96%

“…EBNA3CHT LCLs were cultured and transfected with Ori-P based EBNA3C expression vectors (14,16). Migration assays were performed as described (18).…”

Section: Methodsmentioning

confidence: 99%

“…In medium with 4HT, EBNA3CHT-transformed LCLs grow similarly to wild-type LCLs. In medium without 4HT, EBNA3CHT levels fall substantially by day 7; LCL growth slows after day 7 and stops at day 10-14, when p16 RNA and protein have substantially increased, pRb is hypo-phosphorylated, and cells have accumulated in G0/G1 (14,15). Because EBNA3CHT protein levels are substantially decreased at 7 d in medium without 4HT and LCL growth decreases 1-3 d later, RNA levels were evaluated at day 7, to potentially identify RNA changes that may cause decreased LCL growth and avoid RNA changes that are secondary to slow growth.…”

Section: Ebna3cmentioning

confidence: 99%

“…EBNA3C also 1.4-fold down-regulated p16 and p14 RNAs encoded from the shared CDKN2A exon 2 and 3 probe sets, with FDR <5 × 10 −4 . EBNA3C repression of p16 and p14 is likely central to EBNA3C and EBNA3A combined effects in suppressing these inhibitors of LCL growth (13)(14)(15).…”

Section: Ebna3cmentioning

confidence: 99%

“…Also, activated Notch expression can partially substitute for EBNA2 in maintaining LCL growth (10). Surprisingly, EBNA3A and EBNA3C are each uniquely important for initial and continued LCL growth, whereas EBNA3B is not required (11)(12)(13)(14)(15)(16), although EBNA3B also alters cell gene transcription (17,18). EBNA3C uniquely up-regulates LMP1 (19)(20)(21)(22)(23)(24), CD21(CR2), TCL1A, and ITGA4 expression and represses JAG1, NCALD, p16, BIM, and FLNA expression (14-16, 18, 19, 25, 26).…”

mentioning

confidence: 99%

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Epstein–Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines

Mar¹,

Maruo

Lee

et al. 2010

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

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EBV nuclear antigen 3C (EBNA3C) is an essential transcription factor for EBV transformed lymphoblast cell line (LCL) growth. To identify EBNA3C-regulated genes in LCLs, microarrays were used to measure RNA abundances in each of three different LCLs that conditionally express EBNA3C fused to a 4-OH-Tamoxifen-dependent estrogen receptor hormone binding domain (EBNA3CHT). At least three RNAs were assayed for each EBNA3CHT LCL under nonpermissive conditions, permissive conditions, and nonpermissive conditions with wild-type EBNA3C transcomplementation. Using a two-way ANOVA model of EBNA3C levels, we identified 550 regulated genes that were at least 1.5-fold up-or down-regulated with false discovery rates < 0.01. EBNA3C-regulated genes overlapped significantly with genes regulated by EBNA2 and EBNA3A consistent with coordinated effects on cell gene transcription. Of the 550 EBNA3C-regulated genes, 106 could be placed in protein networks. A seeded Bayesian network analysis of the 80 most significant EBNA3C-regulated genes suggests that RAC1, LYN, and TNF are upstream of other EBNA3C-regulated genes. Gene set enrichment analysis found enrichment for MAP kinase signaling, cytokine-cytokine receptor interactions, JAK-STAT signaling, and cell adhesion molecules, implicating these pathways in EBNA3C effects on LCL growth or survival. EBNA3C significantly up-regulated the CXCL12 ligand and its CXCR4 receptor and increased LCL migration. CXCL12 up-regulation depended on EBNA3C's interaction with the cell transcription factor, RBPJ, which is essential for LCL growth. EBNA3C also up-regulated MYC 1.3-fold and down-regulated CDKN2A exons 2 and 3, shared by p16 and p14, 1.4-fold, with false discovery rates < 5 × 10 −4 . lymphoma | Notch

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Section: Ebna3c-regulated Genes Overlap With Ebna2-and Ebna3a-regulatedmentioning

confidence: 96%

“…EBNA3CHT LCLs were cultured and transfected with Ori-P based EBNA3C expression vectors (14,16). Migration assays were performed as described (18).…”

Section: Methodsmentioning

confidence: 99%

Section: Ebna3cmentioning

confidence: 99%

Section: Ebna3cmentioning

confidence: 99%

mentioning

confidence: 99%

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Epstein–Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines

Mar¹,

Maruo

Lee

et al. 2010

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

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Herpesviruses

Cohen

2017

Holland‐Frei Cancer Medicine

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Overview Eight herpesviruses have been isolated from humans: two of these, Epstein–Barr virus (EBV) and Kaposi sarcoma‐associated herpesvirus (KSHV), are associated with human tumors. EBV has been detected in lesions from patients with post‐transplant lymphoproliferative disease, nasopharyngeal and some types of gastric carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and certain other lymphoid tumors. KSHV is associated with Kaposi sarcoma, primary effusion lymphoma, and Castleman disease. Each of these viruses encodes proteins important for establishment of latency, transforming cells, and evading the immune system.

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Herpesviruses

Cohen¹

2022

Holland‐Frei Cancer Medicine

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Overview Eight herpesviruses have been isolated from humans: two of these, Epstein–Barr virus (EBV), and Kaposi sarcoma‐associated herpesvirus (KSHV), are associated with human tumors. EBV has been detected in lesions from patients with posttransplant lymphoproliferative disease, nasopharyngeal and some types of gastric carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and certain other lymphoid tumors. KSHV is associated with Kaposi sarcoma, primary effusion lymphoma, and Castleman disease. Each of these viruses encodes proteins important for establishment of latency, transforming cells, and evading the immune system.

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Epstein–Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells

Abstract: Epstein-Barr virus (EBV) infection converts primary human B cells into continuously proliferating lymphoblastoid cell lines (LCLs

Cited by 94 publications

References 45 publications

Epstein–Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines

Epstein–Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines

Herpesviruses

Herpesviruses

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