Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model

Ng, Han Leng; Taylor, Rhonda L.; Cheng, Jessica; Abraham, Lawrence J.; Quail, Elizabeth; Cruickshank, Mark N; Ulgiati, Daniela

doi:10.1016/j.molimm.2020.10.001

Cited by 3 publications

(2 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that CR2 upregulation by MYC occurs at the first stages of cell transformation into BL cell and is not maintained in subsequent advanced stages. Also, there are other transcription factors known to regulate CR2 expression [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, and enhances the viral infection of Burkitt lymphoma cells

Molina

García-Gutiérrez

Junco

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The molecular hallmark of Burkitt lymphoma (BL) is a chromosomal translocation that results in deregulated expression of MYC oncogene. This translocation is present in virtually all BL. MYC is an oncogenic transcription factor deregulated in about half of total human tumors, by translocation or other mechanisms. Transcriptomic studies reveal more than 1000 genes regulated by MYC but a much smaller fraction of these genes is directly activated by MYC. All the endemic BL and many sporadic BL cells are associated to the Epstein-Barr virus (EBV) infection. The currently accepted mechanism for the MYC and BL association is that EBV is the causing agent inducing MYC translocation. Complement receptor 2 or CR2 (also called CD21) is a membrane protein that serves as EBV receptor in lymphoid cells. Here we show that CR2 is a direct MYC target gene. This conclusion is based on several evidences. First, MYC downregulation is linked to CR2 downregulation both in proliferating and in arrested cells. Second, MYC binds human CR2 promoter and this binding depends on E-box elements. Third, MYC activates CR2 promoter in an E-box dependent manner. Four, MYC activates CR2 transcription in the absence of protein synthesis. Importantly, MYC also induces CR2 expression in mouse primary B cells. Thus, CR2 is a bona fide MYC direct target gene. Moreover, higher MYC expression levels in Burkitt lymphoma-derived cells result in a more efficient EBV infection. We propose an alternative mechanism compatible with the correlation between EBV infection and MYC translocation observed in endemic BL, i.e., that deregulated MYC in BL cells occurs first and favors the EBV infection.

show abstract

Section: Discussionmentioning

confidence: 99%

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, and enhances the viral infection of Burkitt lymphoma cells

Molina

García-Gutiérrez

Junco

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent data from our laboratory has demonstrated a role for Notch signaling in mediating transcription of the mature B cell marker, Complement Receptor 2 (CR2), in pre-B cells [56]. However, the molecular mechanism of Notch signaling during the pre-B to mature B cell transition remains to be fully elucidated.…”

Section: Notch Signal Involvement From Hematopoietic Stem Cells To B Lymphocytesmentioning

confidence: 99%

To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis

Quail

Cruickshank

et al. 2021

Biomolecules

Self Cite

View full text Add to dashboard Cite

Notch signaling forms an evolutionarily conserved juxtacrine pathway crucial for cellular development. Initially identified in Drosophila wing morphogenesis, Notch signaling has since been demonstrated to play pivotal roles in governing mammalian cellular development in a large variety of cell types. Indeed, abolishing Notch constituents in mouse models result in embryonic lethality, demonstrating that Notch signaling is critical for development and differentiation. In this review, we focus on the crucial role of Notch signaling in governing embryogenesis and differentiation of multiple progenitor cell types. Using hematopoiesis as a diverse cellular model, we highlight the role of Notch in regulating the cell fate of common lymphoid progenitors. Additionally, the influence of Notch through microenvironment interplay with lymphoid cells and how dysregulation influences disease processes is explored. Furthermore, bi-directional and lateral Notch signaling between ligand expressing source cells and target cells are investigated, indicating potentially novel therapeutic options for treatment of Notch-mediated diseases. Finally, we discuss the role of cis‑inhibition in regulating Notch signaling in mammalian development.

show abstract

MYC directly transactivates CR2/CD21, the receptor of the Epstein–Barr virus, enhancing the viral infection of Burkitt lymphoma cells

Molina,

García-Gutiérrez,

Junco

et al. 2023

Oncogene

Self Cite

View full text Add to dashboard Cite

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors.Transcriptomic studies reveal more than 1000 genes regulated by MYC but a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. All endemic BL and a fraction of sporadic BL are associated to Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the lymphoma causing agent inducing MYC translocation. Herein we show that the EBV receptor gene, CR2 (or CD21), is a bona fide direct MYC target gene. This is based on several evidences: MYC induces CR2 expression in both proliferating and arrested cells, binds the human CR2 promoter and transactivates CR2 in an E-box dependent manner and in the absence of protein synthesis. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, MYC silencing or MYC overexpression in BL cells results in less and more efficient EBV infection, respectively. Altogether, in contrast to the widely accepted mechanism for the correlation between EBV and endemic BL, we propose an alternative mechanism in which MYC dysregulation occurs first and favors the EBV infection.

show abstract

Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model

Cited by 3 publications

References 61 publications

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, and enhances the viral infection of Burkitt lymphoma cells

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, and enhances the viral infection of Burkitt lymphoma cells

To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis

MYC directly transactivates CR2/CD21, the receptor of the Epstein–Barr virus, enhancing the viral infection of Burkitt lymphoma cells

Contact Info

Product

Resources

About