RNF4型
泛素连接酶
泛素
相扑蛋白
蛋白酶体
细胞生物学
早幼粒细胞白血病蛋白
DDB1型
化学
生物
生物化学
分子生物学
急性早幼粒细胞白血病
维甲酸
锌指
转录因子
基因
作者
Michael H. Tatham,Marie‐Claude Geoffroy,Linnan Shen,Anna Plechanovová,Neil Hattersley,Ellis Jaffray,Jorma J. Palvimo,Ronald T. Hay
摘要
In acute promyelocytic leukaemia (APL), the promyelocytic leukaemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation. Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro. In the absence of RNF4, arsenic failed to induce degradation of PML and SUMO-modified PML accumulated in the nucleus. These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis.
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