核酸生物合成和脱化介导的糖解被瘤性疹病毒劫持
Quanyuan Wan1, Leah Tavakoli1, Ting-Yu Wang2,3
1Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, USA.
Nature communications
|February 16, 2024
概括
卡波西卡波西 (Kaposi Kaposi) 是一个
科学领域:
- 病毒学和癌症生物学 病毒学和癌症生物学
- 在病毒瘤发生过程中代谢重编程
背景情况:
- 卡波西肉瘤相关的疹病毒 (KSHV) 驱动卡波西肉瘤和B细胞恶性瘤.
- KSHV改变宿主新陈代谢,有助于病毒的持久性和瘤形成,但机制尚不清楚.
- 碳酸合成酶2,酸转碳酸酶和二基酶 (CAD) 酶对于胺合成至关重要,并且与促进有氧糖解有关.
研究的目的:
- 阐明KSHV重编程宿主细胞代谢的机制.
- 研究CAD酶在KSHV驱动的代谢变化和瘤发生中的作用.
- 探索针对KSHV诱导的代谢重编程的治疗策略.
主要方法:
- 研究了KSHVvCyclin和CDK6.6之间的相互作用.
- 通过CDK6.6对CAD在Ser-1900的酸化进行分析.
- 利用基因枯竭和药理上抑制CDK6和CAD.
- 在体外和体内评估了对KSHV溶性复制和PEL细胞瘤发生的影响.
主要成果:
- KSHV感染激活了用于核酸合成和糖解的CAD.
- KSHV vCyclin劫持了CDK6以酸化和激活CAD,从而促进了pyrimidine合成.
- 激活的CAD除化RelA,驱动糖溶性重编程和细胞增殖.
- 抑制CDK6或CAD抑制了KSHV复制和PEL细胞瘤发生.
结论:
- 通过CDK6,KSHV利用CAD酶进行核酸合成和糖解.
- 这种病毒代谢重编程对于KSHV的瘤发生至关重要.
- 向CDK6和CAD为KSHV相关的恶性瘤提供了潜在的治疗途径.
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