EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes.
Epstein-Barr virus (EBV), like other DNA tumor viruses, induces an S-phase in the natural host cell, the human B lymphocyte. This is linked with blast transformation. It is believed that the EBV-encoded nuclear antigen 6 (EBNA-6) is involved in the regulation of cell cycle entry. However, the possible mechanism of this regulation is not approached. In our current study, we found that EBNA-6 binds to a MRPS18-2 protein, and targets it to the nucleus. We found that MRPS18-2 binds to both hypo- and hyperphosphorylated forms of Rb protein specifically. This binding targets the small pocket of pRb, which is a site of interaction with E2F1. The MRPS18-2 competes with the binding of E2F1 to pRb, thereby raising the level of free E2F1. Our experimental data suggest that EBNA-6 may play a major role in the entry of EBV infected B cells into the S phase by binding to and raising the level of nuclear MRPS18-2, protein. This would inhibit pRb binding to E2F1 competitively and lift the block preventing S-phase entry.
Kashuba
Elena
E
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Box 280, Stockholm, S-17177 Sweden. elena.kashuba@ki.se
Yurchenko
Mariya
M
Yenamandra
Surya Pavan
SP
Snopok
Boris
B
Isaguliants
Maria
M
Szekely
Laszlo
L
Klein
George
G
D021581:Active Transport, Cell Nucleus; D000956:Antigens, Viral / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D018076:DNA, Complementary; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000737:chemistry; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D014162:Transfection
D000956:Antigens, Viral; D018076:DNA, Complementary; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C529274:EBNA-6 protein, human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D016160:Retinoblastoma Protein; D012269:Ribosomal Proteins; C041184:ribosomal protein S18