Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry.
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry.
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DOI：
10.1038/s41467-023-35874-w
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发表时间：
2023-01-23
影响因子：
16.6
通讯作者：
Schelhaas, Mario
中科院分区：
文献类型：
--
作者：
Rizzato, Matteo;Mao, Fuxiang;Chardon, Florian;Lai, Kun-Yi;Villalonga-Planells, Ruth;Drexler, Hannes C. A.;Pesenti, Marion E. E.;Fiskin, Mert;Roos, Nora;King, Kelly M. M.;Li, Shuaizhi;Gamez, Eduardo R. R.;Greune, Lilo;Dersch, Petra;Simon, Claudia;Masson, Murielle;Van Doorslaer, Koenraad;Campos, Samuel K. K.;Schelhaas, Mario
有丝分裂诱导细胞重排，如纺锤体形成、高尔基体断裂和核膜破裂。与某些逆转录病毒类似，有丝分裂促进人乳头瘤病毒 (HPV) 基因组进入过程中的核传递，在此过程中，次要衣壳蛋白 L2 将病毒 DNA 束缚在有丝分裂染色体上。然而，人们对病毒基因组传递和束缚染色体的机制知之甚少。目前尚不清楚哪些细胞蛋白促进这一过程或该过程是如何调节的。这项工作鉴定了有丝分裂开始时发生的 HPV 次要衣壳蛋白 L2 的关键磷酸化。 L2 的染色体结合区 (CBR) 依次被主有丝分裂激酶 CDK1 和 PLK1 磷酸化。因此，L2 磷酸化在有丝分裂过程中调节 HPV vDNA 及时递送至有丝分裂染色质。总之，我们的工作证明了有丝分裂激酶对于病毒 DNA 核递送的关键作用，并为有丝分裂期间病原体输入细胞核的分子机制提供了重要见解。人乳头瘤病毒 (HPV) 通过将病毒 DNA 束缚在有丝分裂染色体上来选择有丝分裂进入核，这一过程由病毒次要衣壳蛋白 L2 促进。在这里，里扎托等人。显示L2在染色体结合区域内含有保守的磷酸化基序，并提供证据表明宿主主有丝分裂激酶CDK1和PLK1在有丝分裂开始时顺序介导L2的磷酸化，以允许病毒DNA及时束缚到有丝分裂染色体。
Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis. Human papillomavirus (HPV) coopts mitosis for nuclear entry by tethering the viral DNA to mitotic chromosomes, a process facilitated by the viral minor capsid protein L2. Here, Rizzato et al. show that L2 contains conserved phosphorylation motifs within the chromosome-binding region and provide evidence that host master mitotic kinases CDK1 and PLK1 sequentially mediate phosphorylation of L2 at mitosis onset to allow timely tethering of viral DNA to mitotic chromosomes.
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影响因子：
64.5
作者：
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通讯作者：
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