Molecular Mechanisms of TNFR-associated Factor 6 (TRAF6) Utilization by the Oncogenic Viral Mimic of CD40, Latent Membrane Protein 1 (LMP1)

Arcipowski, Kelly M.; Stunz, Laura L.; Graham, John; Kraus, Zachary J.; Bush, Tony J. Vanden; Bishop, Gail A.

doi:10.1074/jbc.m110.185983

Cited by 46 publications

(141 citation statements)

References 62 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Ubiquitination or deubiquitination of key signaling molecules is an important regulatory mechanism in NF-B signaling. It is known that TRAF6 is an especially critical host factor for LMP1-mediated B cell activation, and its ubiquitination activates NF-B signaling in latently infected cells (20). Therefore, we set out to examine whether BPLF1 could target TRAF6 to suppress NF-B signaling.…”

Section: Ectopic Expression Of Bplf1 Decreases Nf-b-responsive Promotmentioning

confidence: 99%

See 1 more Smart Citation

Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-κB Signaling during Productive Replication

Saito

Murata

Kanda

et al. 2013

J Virol

View full text Add to dashboard Cite

Epstein-Barr virus (EBV), a human oncogenic herpesvirus that establishes a lifelong latent infection in the host, occasionally enters lytic infection to produce progeny viruses. The EBV oncogene latent membrane protein 1 (LMP1), which is expressed in both latent and lytic infection, constitutively activates the canonical NF-κB (p65) pathway. Such LMP1-mediated NF-κB activation is necessary for proliferation of latently infected cells and inhibition of viral lytic cycle progression. Actually, canonical NF-κB target gene expression was suppressed upon the onset of lytic infection. TRAF6, which is activated by conjugation of polyubiquitin chains, associates with LMP1 to mediate NF-κB signal transduction. We have found that EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. HEK293 cells with BPLF1-deficient recombinant EBV exhibited poor viral DNA replication compared with the wild type. Furthermore, exogenous expression of BPLF1 or p65 knockdown in cells restored DNA replication of BPLF1-deficient viruses, indicating that EBV BPLF1 deubiquitinates TRAF6 to inhibit NF-κB signal transduction, leading to promotion of viral lytic DNA replication.

show abstract

Section: Ectopic Expression Of Bplf1 Decreases Nf-b-responsive Promotmentioning

confidence: 99%

“…The IKK complexes phosphorylate and promote proteasomal degradation of IB, resulting in release of NF-B from the inhibitor complex. It was recently demonstrated that TRAF6 associates with the CTAR1 subdomain of LMP1 and is critical for LMP1-mediated activation of NF-B signaling (5,20). TRAF6 activates IKK in a K63-ubiquitin (Ub) chain-dependent manner.…”

mentioning

confidence: 99%

Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-κB Signaling during Productive Replication

Saito

Murata

Kanda

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…This allowed us, for the first time, to directly compare CD40 versus LMP1 requirements for specific TRAFs in B cell activation. To our considerable surprise, we subsequently found that LMP1 utilizes each of the TRAFs in a manner quite distinct from the ways these same TRAFs are used by CD40 (33)(34)(35)(36)(37)(38).…”

mentioning

confidence: 99%

The Many Faces of TRAF Molecules in Immune Regulation

Bishop

2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

“…The abnormal expression of both CD40 and CD40L on B-cell-originated malignant cells is involved in the development of tumors. The interaction of CD40 and CD40L is used in cell transformation in many carcinogens, such as in viral infections [14]. Whether the CD40L provided by these cells or the upregulation of CD40L enables the survival of malignant B cells, which normally cannot enter the T-celldependent pathway in the GC, remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

Ye-wei

Zhao

et al. 2012

Sci. China Life Sci.

View full text Add to dashboard Cite

Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections, such as Epstein-Barr virus. Epstein-Barr virus is a γ-herpesvirus and is related to many malignant diseases, especially epithelial and lymph tumors. The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells. This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation. Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells. Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos. 5, 8, 9, and 10, particularly in sample No. 5. Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus. The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro. Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells, which may be involved in the anti-apoptosis activity of the infected cells. Confocal microscopy showed that pairs of molecules of cluster of differentiation 40, cluster of differentiation 40 ligand, and latent membrane protein 1 were colocalized on the surface of the infected cells. CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection. The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α. Anti-apoptosis and migration are known important biological characteristics of malignant cells. Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma. The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center, which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.

show abstract

Molecular Mechanisms of TNFR-associated Factor 6 (TRAF6) Utilization by the Oncogenic Viral Mimic of CD40, Latent Membrane Protein 1 (LMP1)

Cited by 46 publications

References 62 publications

Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-κB Signaling during Productive Replication

Epstein-Barr Virus Deubiquitinase Downregulates TRAF6-Mediated NF-κB Signaling during Productive Replication

The Many Faces of TRAF Molecules in Immune Regulation

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

Contact Info

Product

Resources

About