EBNA-5, AN EPSTEIN-BARR VIRUS-ENCODED NUCLEAR ANTIGEN, BINDS TO THE RETINOBLASTOMA AND P53 PROTEINS

EBNA-5, AN EPSTEIN-BARR VIRUS-ENCODED NUCLEAR ANTIGEN, BINDS TO THE RETINOBLASTOMA AND P53 PROTEINS
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DOI:
10.1073/pnas.90.12.5455
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发表时间:
1993-06-15
影响因子:
11.1
通讯作者:
WIMAN, KG
WIMAN, KG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SZEKELY, L;SELIVANOVA, G;WIMAN, KG

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EB病毒(EBV)永生化的人淋巴母细胞样细胞系表达六种病毒编码的核蛋白,称为EBV核抗原1-6(EBNA-1-6)。我们表明,EBNA-5蛋白(也称为EBNA-LP)是B细胞转化所需的,可以形成一个分子复合物与视网膜母细胞瘤(RB)和p53肿瘤抑制蛋白。使用EBNA-5缺失突变体,我们发现由EBV基因组的W重复序列编码的66个氨基酸长的肽足以结合。抑制RB和p53与其他DNA病毒癌蛋白复合的点突变不影响它们与EBNA-5的结合。p53与RB竞争EBNA-5结合。我们的数据表明,EBV转化的机制可能包括RB和p53功能的损害。
Epstein-Barr virus (EBV) immortalized human lymphoblastoid cell lines express six virally encoded nuclear proteins, designated EBV nuclear antigens 1-6 (EBNA-1-6). We show that the EBNA-5 protein (alternatively designated EBNA-LP) that is required for B-cell transformation can form a molecular complex with the retinoblastoma (RB) and p53 tumor suppressor proteins. Using EBNA-5 deletion mutants, we have found that a 66-amino acid-long peptide, encoded by the W repeat of the EBV genome, is sufficient for binding. Point mutations of RB and p53 that inhibit their complexing with other DNA viral oncoproteins do not affect their binding to EBNA-5. p53 competes with RB for EBNA-5 binding. Our data suggest that the mechanisms involved in EBV transformation may include impairment of RB and p53 function.