Platt G M, Cannell E, Cuomo M E, Singh S, Mittnacht S
Centre for Cell and Molecular Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, United Kingdom.
Virology. 2000 Jul 5;272(2):257-66. doi: 10.1006/viro.2000.0343.
The human herpesvirus 8 (HHV8/KSHV), along with certain other herpesviruses, encodes a gene with cyclin homology. Although the functional significance of the encoded cyclin is not clear at present, various lines of evidence propose a role for this cyclin in latently infected cells and possibly in the induction of tumors that arise in HHV8-infected individuals. We provide evidence here that the cyclin protein is expressed in HHV8 positive primary effusion lymphoma (PEL)-derived cell lines and that its level of expression varies greatly between different lines. Our analysis indicates that the level of cyclin protein expression in different PEL cell lines may correlate with the level of transcript expression during latency but not in cells induced to undergo lytic replication. In highly expressing BC-3 cells the cyclin is complexed with cdk6, cdk4, cdk2, and cdk5 under both latent and lytic conditions, although subtle changes in the level of cdk association are seen after induction of the lytic cycle. Altogether our findings support the notion that the cyclin is a latency-associated gene product expressed in PEL tumor cells. They furthermore indicate that after lytic cycle induction, the level of cyclin transcript expression may not be a reliable indicator for the level of cyclin protein expression.
人类疱疹病毒8型(HHV8/KSHV)与某些其他疱疹病毒一样,编码一种具有细胞周期蛋白同源性的基因。尽管目前编码的细胞周期蛋白的功能意义尚不清楚,但各种证据表明该细胞周期蛋白在潜伏感染的细胞中发挥作用,并且可能在HHV8感染个体中出现的肿瘤诱导中发挥作用。我们在此提供证据表明,细胞周期蛋白在HHV8阳性原发性渗出性淋巴瘤(PEL)来源的细胞系中表达,并且其表达水平在不同细胞系之间差异很大。我们的分析表明,不同PEL细胞系中细胞周期蛋白的表达水平可能与潜伏期间的转录本表达水平相关,但在诱导进行裂解复制的细胞中则不然。在高表达的BC-3细胞中,无论在潜伏还是裂解条件下,细胞周期蛋白都与细胞周期蛋白依赖性激酶6(cdk6)、细胞周期蛋白依赖性激酶4(cdk4)、细胞周期蛋白依赖性激酶2(cdk2)和细胞周期蛋白依赖性激酶5(cdk5)形成复合物,尽管在诱导裂解周期后,细胞周期蛋白依赖性激酶的结合水平会出现细微变化。总之,我们的研究结果支持细胞周期蛋白是一种在PEL肿瘤细胞中表达的潜伏相关基因产物这一观点。此外,研究结果还表明,在诱导裂解周期后,细胞周期蛋白转录本的表达水平可能不是细胞周期蛋白表达水平的可靠指标。