Iwahori Satoko, Kalejta Robert F
Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, United States.
Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, United States.
Virology. 2017 Dec;512:95-103. doi: 10.1016/j.virol.2017.09.009.
Human cytomegalovirus (HCMV) encodes a viral cyclin-dependent kinase (v-CDK), the UL97 protein. UL97 phosphorylates Rb, p107 and p130, thereby inactivating all three retinoblastoma (Rb) family members. Rb proteins function through regulating the activity of transcription factors to which they bind. Therefore, we examined whether the UL97-mediated regulation of the Rb tumor suppressors also extended to their binding partners. We observed that UL97 phosphorylates LIN52, a component of p107- and p130-assembled transcriptionally repressive DREAM complexes that control transcription during the G0/G1 phases, and the Rb-associated E2F3 protein that activates transcription through G1 and S phases. Intriguingly, we also identified FoxM1B, a transcriptional regulator during the S and G2 phases, as a UL97 substrate. This survey extends the influence of UL97 beyond simply the Rb proteins themselves to their binding partners, as well as past the G1/S transition into later stages of the cell cycle.
人类巨细胞病毒（HCMV）编码一种病毒细胞周期蛋白依赖性激酶（v-CDK），即UL97蛋白。UL97使Rb、p107和p130磷酸化，从而使所有三个视网膜母细胞瘤（Rb）家族成员失活。Rb蛋白通过调节与其结合的转录因子的活性发挥作用。因此，我们研究了UL97介导的对Rb肿瘤抑制因子的调节是否也扩展到了它们的结合伙伴。我们观察到UL97使LIN52磷酸化，LIN52是在G0/G1期控制转录的由p107和p130组装而成的转录抑制性DREAM复合物的一个组成部分，以及通过G1和S期激活转录的与Rb相关的E2F3蛋白。有趣的是，我们还确定了在S期和G2期的转录调节因子FoxM1B是UL97的一个底物。这项研究将UL97的影响范围从单纯的Rb蛋白本身扩展到了它们的结合伙伴，以及从G1/S期过渡到细胞周期的后期阶段。
