title: Epstein-Barr virus-encoded EBNA-5 binds to Epstein-Barr virus-induced Fte1/S3a protein.
abstract: Epstein-Barr virus (EBV) transforms resting human B cells into immortalized immunoblasts. EBV-encoded nuclear antigens EBNA-5 (also called EBNA-LP) is one of the earliest viral proteins expressed in freshly infected B cells. We have recently shown that EBNA-5 binds p14ARF, a nucleolar protein that regulates the p53 pathway. Here, we report the identification of another protein with partially nucleolar localization, the v-fos transformation effector Fte-1 (Fte-1/S3a), as an EBNA-5 binding partner. In transfected cells, Fte-1/S3a and EBNA-5 proteins showed high levels of colocalization in extranucleolar inclusions. Fte-1/S3a has multiple biological functions. It enhances v-fos-mediated cellular transformation and is part of the small ribosomal subunit. It also interacts with the transcriptional factor CHOP and apoptosis regulator poly(ADP-ribose) polymerase (PARP). Fte-1/S3a is regularly expressed at high levels in both tumors and cancer cell lines. Its high expression favors the maintenance of malignant phenotype and undifferentiated state, whereas its down-regulation is associated with cellular differentiation and growth arrest. Here, we show that EBV-induced B cell transformation leads to the up-regulation of Fte-1/S3a. We suggest that EBNA-5 through binding may influence the growth promoting, differentiation inhibiting, or apoptosis regulating functions of Fte-1/S3a.
authors.affiliation: Microbiology and Tumor Biology Center (MTC), S-171 77 Stockholm, Sweden. Elena.Kashuba@mtc.ki.se
authors.forename: Elena
authors.initials: E
authors.lastname: Kashuba
authors.forename: Mariya
authors.initials: M
authors.lastname: Yurchenko
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szirak
authors.forename: Joachim
authors.initials: J
authors.lastname: Stahl
authors.forename: George
authors.initials: G
authors.lastname: Klein
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szekely
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000378:metabolism*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; C421621:EBNA-5 protein, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C031016:RPS3A protein, human; D012269:Ribosomal Proteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D011065:Poly(ADP-ribose) Polymerases