Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation.
Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation.
复制标题
DOI：
10.1016/j.virol.2013.02.014
复制
发表时间：
2013-06-05
期刊：
影响因子：
3.7
通讯作者：
Ling PD
中科院分区：
文献类型：
--
作者：
Sewatanon J;Ling PD
所有的伽马疱疹病毒都编码至少一个与细胞甲酰甘氨酰胺核糖核酸氨基转移酶(FGARAT)相关的基因，但它们的生物学作用相对未知。小鼠伽马疱疹病毒68(MHV68)vFGARAT，ORF75c，通过一种未知的机制介导蛋白酶体依赖的抗病毒早幼粒细胞白血病(PML)蛋白的降解，本研究对此进行了研究。我们发现ORF75c与PML的相互作用很弱，PML的相扑修饰形式对ORF75c降解PML很重要。ORF75c介导的PML降解不依赖于两种已知的PML稳定性细胞调节因子--酪蛋白激酶II(CK2)和人乳头瘤病毒E6相关蛋白(E6AP)。最后，ORF75c在体外具有自身泛素化活性，其表达增加了转染细胞中泛素化PML的水平。综上所述，本研究积累的证据为vFGARAT的功能提供了新的见解，并与ORF75c可能介导PML的直接泛素化导致其被蛋白酶体降解的模型一致。
All gammaherpsviruses encode at least one gene related to the cellular formylglycinamide ribonucleotide amidotransferase (FGARAT) enzyme but their biological roles are relatively unknown. The murine gammaherpesvirus 68 (MHV68) vFGARAT, ORF75c, mediates a proteasome-dependent degradation of the antiviral promyelocytic leukemia (PML) protein by an unknown mechanism, which is addressed in this study. We found that ORF75c interacts weakly with PML and SUMO-modified forms of PML are important for its degradation by ORF75c. ORF75c-mediated PML degradation was not dependent on two known cellular regulators of PML stability, Casein kinase II (CK2) and human papilloma virus E6-associated protein (E6AP). Finally, ORF75c had self-ubiquitination activity in vitro and its expression increased levels of ubiquitinated PML in transfected cells. Taken together, the evidence accumulated in this study provides new insights into the function of a vFGARAT and is consistent with a model in which ORF75c could mediate direct ubiquitination of PML resulting in its degradation by the proteasome.
登录
查看更多内容
病毒的泛素连接酶具有抵抗内在抗病毒药防御的底物优先SUMO靶向泛素连接酶活性。
影响因子：
6.7
作者：
Boutell C;Cuchet-Lourenço D;Vanni E;Orr A;Glass M;McFarlane S;Everett RD
通讯作者：
Everett RD
ORF75c 在鼠疱疹病毒 4 感染中的多种功能。
影响因子：
3.7
作者：
Gaspar, Miguel;Gill, Michael B.;Loesing, Jens-Bernhard;May, Janet S.;Stevenson, Philip G.
通讯作者：
Stevenson, Philip G.
影响因子：
12.4
作者：
Louria-Hayon, I.;Alsheich-Bartok, O.;Haupt, Y.
通讯作者：
Haupt, Y.
影响因子：
5.4
作者：
Ahn, JH;Hayward, GS
通讯作者：
Hayward, GS
影响因子：
4
作者：
Evdokimov, Evgenij;Sharma, Prashant;Kuehn, Michael R.
通讯作者：
Kuehn, Michael R.