Borden K L, CampbellDwyer E J, Salvato M S
Department of Biochemistry, Dalhousie University, Halifax, N.S., Canada.
FEBS Lett. 1997 Nov 24;418(1-2):30-4. doi: 10.1016/s0014-5793(97)01344-6.
The promyelocytic leukemia protein PML is known to form nuclear multiprotein complexes which are compromised in several pathogenic conditions including acute promyelocytic leukemia. We show that in cells infected with a single stranded RNA virus, which relocates PML bodies to the cytoplasm, the infected cells are more resistant to serum starvation induced apoptosis than their uninfected counterparts. Antisense PML oligonucleotides increase cell survival under serum deprivation conditions indicating that PML is directly involved in the apoptotic activity. Transient transfection studies have indicated that this pro-apoptotic activity of PML is mediated through the zinc binding region known as the RING finger. Viral attack of PML nuclear bodies appears to allow the virus to deregulate host cell apoptotic machinery in order to establish chronic infection.
早幼粒细胞白血病蛋白PML已知可形成核多蛋白复合物,在包括急性早幼粒细胞白血病在内的几种致病条件下,这些复合物会受到损害。我们发现,在感染单链RNA病毒的细胞中,PML小体重新定位于细胞质,与未感染的对应细胞相比,感染细胞对血清饥饿诱导的凋亡更具抗性。反义PML寡核苷酸在血清剥夺条件下可提高细胞存活率,表明PML直接参与凋亡活性。瞬时转染研究表明,PML的这种促凋亡活性是通过称为环指的锌结合区域介导的。PML核小体的病毒攻击似乎使病毒能够解除宿主细胞凋亡机制的调控,从而建立慢性感染。