Abstract:
Dysregulation of the constitutive heterochromatin machinery (HCM) that silences pericentromeric regions and endogenous retroviral elements in the human genome has consequences for aging and cancer. By recruiting epigenetic regulators, Krüppel-associated box (KRAB)-associated protein 1 (KAP1/TRIM28/TIF1β) is integral to the function of the HCM. Epigenetically silencing DNA genomes of incoming herpesviruses to enforce latency, KAP1 and HCM also serve in an antiviral capacity. In addition to gene silencing, newer reports highlight KAP1\'s ability to directly activate cellular gene transcription. Here, we discuss the many facets of KAP1, including recent findings that unexpectedly connect KAP1 to the inflammasome, reveal KAP1 cleavage as a novel mode of regulation, and argue for a pro-herpesviral KAP1 function that ensures transition from transcription to replication of the herpesvirus genome.
摘要:
使人类基因组中的着丝粒周区域和内源性逆转录病毒元件沉默的组成性异染色质机制(HCM)的失调会导致衰老和癌症。通过招募表观遗传调节因子,Krüppel相关盒(KRAB)相关蛋白1(KAP1/TRIM28/TIF1β)是HCM功能不可或缺的部分。表观遗传沉默传入疱疹病毒的DNA基因组,以实施潜伏期,KAP1和HCM也具有抗病毒能力。除了基因沉默,较新的报道强调了KAP1直接激活细胞基因转录的能力。这里,我们讨论了KAP1的许多方面,包括最近的发现,这些发现意外地将KAP1与炎症小体联系起来,揭示KAP1裂解是一种新的调控模式,并主张前疱疹病毒KAP1功能可确保疱疹病毒基因组从转录过渡到复制。