Autocleavage of the paracaspase MALT1 at Arg-781 attenuates NF-κB signaling and regulates the growth of activated B-cell like diffuse large B-cell lymphoma cells.

MALT1 controls several receptors-mediated signaling to nuclear factor κB (NF-κB) through both its scaffold and protease function. MALT1 protease activity is shown to inactivate several negative regulators of NF-κB signaling and augment NF-κB activation ability. In this study, MALT1 was demonstrated to autoprocess itself in the presence of oligomerization-competent BCL10.

Maintenance of Epstein-Barr Virus Latent Status by a Novel Mechanism, Latent Membrane Protein 1-Induced Interleukin-32, via the Protein Kinase Cδ Pathway.

Unlabelled: Epstein-Barr virus (EBV), an oncogenic herpesvirus, has the potential to immortalize primary B cells into lymphoblastoid cell lines (LCLs) in vitro. During immortalization, several EBV products induce cytokines or chemokines, and most of these are required for the proliferation of LCLs. Interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, is upregulated after EBV infection, and this upregulation is detectable in all LCLs tested.

Glycogen synthase kinase 3 negatively regulates IFN regulatory factor 3 transactivation through phosphorylation at its linker region.

Upon virus infection, the host innate immune response is initiated through the activation of IFN regulatory factor 3 (IRF3) and NF-κB signaling pathways to induce IFN production. Previously, we demonstrated EBV BGLF4 kinase suppresses IRF3 function in a kinase activity-dependent manner. The replacement of Ser123, Ser173 and Thr180 into alanines at the proline-rich linker region of IRF3 abolishes BGLF4-mediated suppression.

BCL10GFP fusion protein as a substrate for analysis of determinants required for mucosa-associated lymphoid tissue 1 (MALT1)-mediated cleavage.

Background: MALT1 belongs to a family of paracaspase and modulates NF-κB signaling pathways through its scaffolding function and proteolytic activity. MALT1 cleaves protein substrates after a positively charged Arginine residue. BCL10, a 233 amino acids polypeptide, is identified as one of the MALT1 proteolytic substrates.

Involvement of recepteur d'origine nantais receptor tyrosine kinase in Epstein-Barr virus-associated nasopharyngeal carcinoma and its metastasis.

Nasopharyngeal carcinoma (NPC) is characteristic for its strong association with Epstein-Barr virus (EBV) and high metastatic rate. Recently, overexpressed recepteur d'origine nantais (RON) (MST1R), receptor tyrosine kinase has been reported in human cancers and tumor metastasis. Therefore, the role of RON in EBV-associated NPC and its metastasis was investigated.

Epstein-Barr virus BGLF4 kinase downregulates NF-κB transactivation through phosphorylation of coactivator UXT.

Epstein-Barr virus (EBV) BGLF4 is a member of the conserved herpesvirus kinases that regulate multiple cellular and viral substrates and play an important role in the viral lytic cycles. BGLF4 has been found to phosphorylate several cellular and viral transcription factors, modulate their activities, and regulate downstream events. In this study, we identify an NF-κB coactivator, UXT, as a substrate of BGLF4.

Characterization of Epstein-Barr virus BGLF4 kinase expression control at the transcriptional and translational levels.

The BGLF4 protein of Epstein-Barr virus (EBV) is a serine/threonine protein kinase that phosphorylates several viral and cellular substrates at cellular cyclin-dependent kinase target sites. BGLF4 is required for efficient viral DNA replication and release of mature virions. It also stimulates the transactivation activity of the immediate-early transactivator Zta (BZLF1) and suppresses the transactivation activities of BMRF1 and EBNA-2.

Epstein-Barr virus BGLF4 kinase suppresses the interferon regulatory factor 3 signaling pathway.

The BGLF4 protein kinase of Epstein-Barr virus (EBV) is a member of the conserved family of herpesvirus protein kinases which, to some extent, have a function similar to that of the cellular cyclin-dependent kinase in regulating multiple cellular and viral substrates. In a yeast two-hybrid screening assay, a splicing variant of interferon (IFN) regulatory factor 3 (IRF3) was found to interact with the BGLF4 protein. This interaction was defined further by coimmunoprecipitation in transfected cells and glutathione S-transferase (GST) pull-down in vitro.

Differential expression of osteoblast-specific factor 2 and polymeric immunoglobulin receptor genes in nasopharyngeal carcinoma.

Background: The molecular mechanisms leading to development of nasopharyngeal carcinoma (NPC) are not well understood. To delineate the features of NPC, we tried to identify unique expression of cellular genes in the tumor biopsy specimens.

Methods And Results: By use of a combination of differential display and cDNA microarray analysis, we found two genes, 3E5 and 4A5, to show unique expression in the NPC biopsy specimens compared with nontumor nasopharyngeal tissues.

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma.

Aim: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori (H pylori)-dependent. However, unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors.

Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21).

The t(11;18)(q21;q21) translocation is a specific marker for Helicobacter pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there are no reliable markers to predict tumor response to H pylori eradication in patients without t(11;18)(q21;q21). Nuclear expression of BCL10 and nuclear factor kappa B (NF-kappaB) was recently found to be closely associated with H pylori-independent status of the high-grade counterpart of gastric MALT lymphoma, which usually lacks t(11;18)(q21;q21).

Nuclear expression of BCL10 or nuclear factor kappa B predicts Helicobacter pylori-independent status of early-stage, high-grade gastric mucosa-associated lymphoid tissue lymphomas.

Purpose: A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H. pylori-independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart.

Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference.

Epstein-Barr virus (EBV) reactivation into the lytic cycle plays certain roles in the development of EBV-associated diseases, so an effective strategy to block the viral lytic cycle may be of value to reduce the disease risk or to improve the clinical outcome. This study examined whether the EBV lytic cycle could be inhibited using RNA interference (RNAi) directed against the essential viral gene Zta. In cases of EBV reactivation triggered by chemicals or by exogenous Rta, Zta-targeted RNAi prevented the induction of Zta and its downstream genes and further blocked the lytic replication of viral genomes.

Hepatitis B virus X protein activates a survival signaling by linking SRC to phosphatidylinositol 3-kinase.

We have previously shown that transactivation-proficient hepatitis virus B X protein (HBx) protects Hep 3B cells from transforming growth factor-beta (TGF-beta)-induced apoptosis via activation of the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling pathway. This work further investigated how HBx activates PI 3-kinase. Src activity was elevated in Hep 3B cells following expression of transactivation-proficient HBx or HBx-GFP fusion proteins.

Thyroid hormone receptor alpha 1 (c-erb A alpha 1) suppressed transforming phenotype of nasopharyngeal carcinoma cell line.

Only three thyroid hormone receptor (TR) isoforms, alpha 1, beta 1, and beta 2, bind thyroid hormone (TH) and are considered to be true TRs. TR alpha 2, unable to bind TH, binds to TH response element on DNA and has been shown to exert dominant negative action on TR alpha1. TR alphas regulate many important processes such as proliferation, differentiation and apoptosis.