{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335838/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335838"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A role for the protease MALT1 in EBV-mediated B-cell transformation by Latent Membrane Proteins 1 and 2","description":"Epstein-Barr virus (EBV) is a human herpesvirus that can cause a variety of hematological malignancies, in particular B-, T- and NK-cell lymphomas. Latency proteins of the virus contribute to lymphomagenesis by activating the transcription factor NF-kB, but the molecular mechanism underlying EBV-driven NF-kB activation remains incompletely understood. Here we show that EBV latent membrane proteins LMP1 and LMP2A or LMP2B synergize to activate the protease MALT1, a key driver of NF-kB-mediated lymphocyte proliferation. EBV-positive B-cell lines co-expressing LMP1 and LMP2 proteins exhibited constitutive activity of the protease MALT1, and treatment with a MALT1 inhibitor or silencing of latent membrane protein-1 (LMP1) or LMP2 impaired MALT1-dependent substrate cleavage and proliferation in these cell lines. Further molecular studies revealed that LMP1 physically interacted with the MALT1-binding partner BCL10, while LMP2A and LMP2B interacted with MALT1. LMP1 also colocalized with LMP2 in dotted structures, suggesting that LMP1 and LMP2 synergize via the coordinated formation of LMP-BCL10-MALT1 (LBM) oligomers. Finally, MALT1 protease inhibition led to reduced expression of a set of NF-kB-driven genes, and reduced tumor growth in an EBV-positive lymphoma xenograft model. These findings establish a key role for the protease MALT1 in LMP1/2-mediated, NF-kB-driven cellular transformation and provide a rationale for inhibiting MALT1 to treat EBV-positive B-cell lymphomas that co-express LMP1 and LMP2.","dates":{"publication":"2026/08/17"},"accession":"GSE335838","cross_references":{"GSM":["GSM9821961","GSM9821960","GSM9821956","GSM9821959","GSM9821958","GSM9821957"],"GPL":["34295"],"GSE":["335838"],"taxon":["Homo sapiens"],"PMID":["[42595846]"]}}